AU2023347083A1 - Antiviral sirna therapeutic for sars-cov-2 - Google Patents

Abstract

This disclosure relates to RNA interference (RNAi) reagents for treatment of SARS-CoV-2 infection, compositions comprising same, and use thereof to treat or prevent infection by SARS- CoV-2.

Description

Antiviral siRNA therapeutic for SARS-CoV-2 Technical Field The present disclosure relates to RNA interference (RNAi) reagents for treatment of SARS-CoV-2 infection, compositions comprising same, and use thereof to treat or prevent infection with SARS-CoV-2. Background Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a respiratory virus which causes development of COVID-19 disease and has an estimated global mortality rate of approximately 2%. SARS-CoV-2 infects the respiratory tract, and while many cases result in mild symptoms, severe cases in individuals can result in respiratory failure and death. As of July 2022, there have been >570 million confirmed cases of SARS-CoV-2 and over 6.3 million recorded deaths worldwide. Multiple vaccines and antivirals have been developed and have shown strong protection against early variants, however vaccines are focused on generating responses against Spike, and increasing resistance to emerging variants is reported. Additionally, due to a combination of limited vaccine uptake/availability in many regions, immunocompromised vaccine-non- responders, and people medically exempt from vaccination, additional treatment options are needed. Summary The present disclosure is based, in part, on the recognition that existing vaccines and therapeutic agents for treatment and/or prevention of SARS-CoV-2 infection are limited in their efficacy. The present disclosure provides RNAi reagents targeting one or more conserved regions of RNA transcripts produced by the SARS-CoV-2 genome i.e., regions conserved among a plurality of different variants of SARS-CoV-2. The inventors have shown that these RNAi reagents have an antiviral effect in cells infected with SARS-CoV-2. For example, it has been shown that exemplary RNAi reagents of the disclosure increase cell survival and decrease virus nucleocapsid mRNA and protein levels in Vero E6 cells and HEKAT10 cells harbouring active SARS-CoV-2. These findings by the inventors provide new compounds that inhibit or reduce expression of a nucleic acid and/or protein expressed by SARS-CoV-2 and uses of such compounds e.g., to treat a SARS-CoV-2 infection in a subject. Accordingly, the present disclosure provides a RNA comprising an antisense sequence of at least 19 nucleotides in length and a sense sequence, wherein the antisense sequence is substantially complementary to a RNA transcript encoded by a region of the SARS-CoV-2 genome, wherein the region comprises a sequence set forth in any one of SEQ ID NOs: 1-8. For example, the antisense sequence will be less than 30 nucleotides in length. For example, a suitable antisesense sequence may be in the range of 19-29 nucleotides in length. The antisense sequence may comprise 1 base pair mismatch relative to the sequence set forth in any one of SEQ ID NOs: 1-8 to which the antisense sequence is substantially complementary. In yet another example, the antisense sequence is 100% complementary to a region of equivalent length within a sequence set forth in any one of SEQ ID NOs: 1-8. In one example, the RNA may be selected from the group consisting of: a RNA comprising: (i) an antisense sequence which is complementary to the sequence set forth in SEQ ID NO:10, optionally with the exception of 1 base mismatch, provided that the antisense sequence is capable of forming a duplex with a sequence set forth in SEQ ID NO:10; and (ii) a sense sequence comprising a sequence which is substantially complementary to the antisense sequence; a RNA comprising: (i) an antisense sequence which is complementary to the sequence set forth in SEQ ID NO:12, optionally with the exception of 1 base mismatch, provided that the antisense sequence is capable of forming a duplex with a sequence set forth in SEQ ID NO:12; and (ii) a sense sequence comprising a sequence which is substantially complementary to the antisense sequence; a RNA comprising: (i) an antisense sequence which is complementary to the sequence set forth in SEQ ID NO:14, optionally with the exception of 1 base mismatch, provided that the antisense sequence is capable of forming a duplex with a sequence set forth in SEQ ID NO:14; and (ii) a sense sequence comprising a sequence which is substantially complementary to the antisense sequence; a RNA comprising: (i) an antisense sequence which is complementary to the sequence set forth in SEQ ID NO:16, optionally with the exception of 1 base mismatch, provided that the antisense sequence is capable of forming a duplex with a sequence set forth in SEQ ID NO:16; and (ii) a sense sequence comprising a sequence which is substantially complementary to the antisense sequence; a RNA comprising: (i) an antisense sequence which is complementary to the sequence set forth in SEQ ID NO:18, optionally with the exception of 1 base mismatch, provided that the antisense sequence is capable of forming a duplex with a sequence set forth in SEQ ID NO:18; and (ii) a sense sequence comprising a sequence which is substantially complementary to the antisense sequence; a RNA comprising: (i) an antisense sequence which is complementary to the sequence set forth in SEQ ID NO:20, optionally with the exception of 1 base mismatch, provided that the antisense sequence is capable of forming a duplex with a sequence set forth in SEQ ID NO:20; and (ii) a sense sequence comprising a sequence which is substantially complementary to the antisense sequence; a RNA comprising: (i) an antisense sequence which is complementary to the sequence set forth in SEQ ID NO:22, optionally with the exception of 1 base mismatch, provided that the antisense sequence is capable of forming a duplex with a sequence set forth in SEQ ID NO:22; and (ii) a sense sequence comprising a sequence which is substantially complementary to the antisense sequence; and a RNA comprising: (i) an antisense sequence which is complementary to the sequence set forth in SEQ ID NO:24, optionally with the exception of 1 base mismatch, provided that the antisense sequence is capable of forming a duplex with a sequence set forth in SEQ ID NO:24; and (ii) a sense sequence comprising a sequence which is substantially complementary to the antisense sequence. It will be appreciated that SEQ ID NOs: 10-26 include 3’ dinucleotide overhangs. Any reference herein to the RNA sequences of any one or more of SEQ ID NOs: 10-26 shall be taken to be a reference to the entire sequence of each, and also as a reference to the nucleotide sequence of each but omitting the 3’ dinucleotide overhangs (as set out in Tables 7 and 8). In another example, the RNA may be selected from the group consisting of: a RNA comprising an antisense sequence set forth in SEQ ID NO:9; a RNA comprising an antisense sequence set forth in SEQ ID NO:11; a RNA comprising an antisense sequence set forth in SEQ ID NO:13; a RNA comprising an antisense sequence set forth in SEQ ID NO:15; a RNA comprising an effector secquence set forth in SEQ ID NO:17; a RNA comprising an antisense sequence set forth in SEQ ID NO:19; a RNA comprising an antisense sequence set forth in SEQ ID NO:21; and a RNA comprising an antisense sequence set forth in SEQ ID NO:23. In another example, the RNA may be selected from the group consisting of: a RNA comprising an antisense sequence set forth in SEQ ID NO:9 and a sense sequence which is substantially complementary to the sequence set forth in SEQ ID NO:9 and capable of forming a duplex therewith; a RNA comprising an antisense sequence set forth in SEQ ID NO:11 and a sense sequence which is substantially complementary to the sequence set forth in SEQ ID NO:11 and capable of forming a duplex therewith; a RNA comprising an antisense sequence set forth in SEQ ID NO:13 and a sense sequence which is substantially complementary to the sequence set forth in SEQ ID NO:13 and capable of forming a duplex therewith; a RNA comprising an antisense sequence set forth in SEQ ID NO:15 and a sense sequence which is substantially complementary to the sequence set forth in SEQ ID NO:15 and capable of forming a duplex therewith; a RNA comprising an antisense sequence set forth in SEQ ID NO:17 and a sense sequence which is substantially complementary to the sequence set forth in SEQ ID NO:17 and capable of forming a duplex therewith; a RNA comprising an antisense sequence set forth in SEQ ID NO:19 and a sense sequence which is substantially complementary to the sequence set forth in SEQ ID NO:19 and capable of forming a duplex therewith; a RNA comprising an antisense sequence set forth in SEQ ID NO:21 and a sense sequence which is substantially complementary to the sequence set forth in SEQ ID NO:21 and capable of forming a duplex therewith; and a RNA comprising an antisense sequence set forth in SEQ ID NO:23 and a sense sequence which is substantially complementary to the sequence set forth in SEQ ID NO:23 and capable of forming a duplex therewith. For example, a sense sequence of a RNA of the disclosure may comprise 1, 2, or 3 mismatches relative to the corresponding antisense sequence provided that the cognate antisense sequences and sense sequences are capable of forming a duplex.   In another example, the RNA may be selected from the group consisting of: a RNA comprising an antisense sequence set forth in SEQ ID NO:9 and a sense sequence set forth in SEQ ID NO:10; a RNA comprising an antisense sequence set forth in SEQ ID NO:11 and a sensesequence set forth in SEQ ID NO:12; a RNA comprising an antisense sequence set forth in SEQ ID NO:13 and a sense sequence set forth in SEQ ID NO:14; a RNA comprising an antisense sequence set forth in SEQ ID NO:15 and a sense sequence set forth in SEQ ID NO:16; a RNA comprising an effector secquence set forth in SEQ ID NO:17 and a sense sequence set forth in SEQ ID NO: 18; a RNA comprising an antisense sequence set forth in SEQ ID NO:19 and a sense sequence set forth in SEQ ID NO:20; a RNA comprising an antisense sequence set forth in SEQ ID NO:21 and a sense sequence set forth in SEQ ID NO:22; and a RNA comprising an antisense sequence set forth in SEQ ID NO:23 and a sense sequence set forth in SEQ ID NO:24. In one example, the RNA is a RNAi reagent. The RNA of the disclosure may be provided in the form of a short interfering RNA (siRNA) duplex. In one example, the siRNA duplex comprises: a RNA comprising an antisense sequence set forth in SEQ ID NO:9; a RNA comprising an antisense sequence set forth in SEQ ID NO:11; a RNA comprising an antisense sequence set forth in SEQ ID NO:13; a RNA comprising an antisense sequence set forth in SEQ ID NO:15; a RNA comprising an effector secquence set forth in SEQ ID NO:17; a RNA comprising an antisense sequence set forth in SEQ ID NO:19; a RNA comprising an antisense sequence set forth in SEQ ID NO:21; and a RNA comprising an antisense sequence set forth in SEQ ID NO:23. Alternatively, the RNA of the disclosure may be provided in the form of a short hairpin RNA (shRNA). When provided as a shRNA, the RNA of the disclosure may comprise a loop sequence positioned between the antisense sequence and the sense sequence. Suitable loop sequences may be selected from those known in the art. The RNA of the disclosure may be used in combination. Accordingly, the present disclosure provides a plurality of RNAs, comprising at least one RNA comprising an antisense sequence of at least 19 nucleotides in length and a sense sequence, wherein the antisense sequence is substantially complementary to a RNA transcript encoded by a region of the SARS- CoV-2 genome, wherein the region comprises a sequence set forth in any one of SEQ ID NOs: 1-8. Thus, in one example, the present disclosure provides a plurality of RNAs comprising at least one RNA selected from the group consisting of: a RNA comprising an antisense sequence set forth in SEQ ID NO:9; a RNA comprising an antisense sequence set forth in SEQ ID NO:11; a RNA comprising an antisense sequence set forth in SEQ ID NO:13; a RNA comprising an antisense sequence set forth in SEQ ID NO:15; a RNA comprising an effector secquence set forth in SEQ ID NO:17; a RNA comprising an antisense sequence set forth in SEQ ID NO:19; a RNA comprising an antisense sequence set forth in SEQ ID NO:21; and a RNA comprising an antisense sequence set forth in SEQ ID NO:23. In another example, the present disclosure provides a plurality of RNAs comprising at least one RNA selected from the group consisting of: a RNA comprising an antisense sequence set forth in SEQ ID NO:9 and a sense sequence set forth in SEQ ID NO:10; a RNA comprising an antisense sequence set forth in SEQ ID NO:11 and a sense sequence set forth in SEQ ID NO:12; a RNA comprising an antisense sequence set forth in SEQ ID NO:13 and a sense sequence set forth in SEQ ID NO:14; a RNA comprising an antisense sequence set forth in SEQ ID NO:15 and a sense sequence set forth in SEQ ID NO:16; a RNA comprising an antisense sequence set forth in SEQ ID NO:17 and a sense sequence set forth in SEQ ID NO: 18; a RNA comprising an antisense sequence set forth in SEQ ID NO:19 and a sense sequence set forth in SEQ ID NO:20; a RNA comprising an antisense sequence set forth in SEQ ID NO:21 and a sense sequence set forth in SEQ ID NO:22; and a RNA comprising an antisense sequence set forth in SEQ ID NO:23 and a sense sequence set forth in SEQ ID NO:24. It will be understood by a person of skill in the art that a RNA in accordance with the present disclosure may be combined or used in conjunction with other therapeutic agents for treating SARS-CoV-2. Accordingly, the present disclosure provides a RNA as described herein in combination with one or more other agents for treating SARS-CoV-2. A plurality of RNAs in accordance with the present disclosure may comprise up to eight RNAs, such as two RNAs or three RNAs or four RNAs or five RNAs or six RNAs or seven RNAs or eight RNAs. In one example, the plurality of RNAs comprises at least one of the RNAs described herein. In one example, the plurality of RNAs comprises at least two of the RNAs described herein. In another example, the plurality of RNAs comprises at least three of the RNAs described herein. In one example, the plurality of RNAs comprises at least four of the RNAs described herein. In one example, the plurality of RNAs comprises at least five of the RNAs described herein. In one example, the plurality of RNAs comprises at least six of the RNAs described herein. In one example, the plurality of RNAs comprises at least seven of the RNAs described herein. In one example, the plurality of RNAs comprises eight of the RNAs described herein. Thus, in one example, the plurality of RNAs comprises at least one RNA selected from the group consisting of: (a) a RNA comprising an antisense sequence set forth in SEQ ID NO:9 and a sense sequence set forth in SEQ ID NO:10 and a RNA comprising an antisense sequence set forth in SEQ ID NO:11 and a sense sequence set forth in SEQ ID NO:12; (b) a RNA comprising an antisense sequence set forth in SEQ ID NO:9 and a sense sequence set forth in SEQ ID NO:10 and a RNA comprising an antisense sequence set forth in SEQ ID NO:13 and a sense sequence set forth in SEQ ID NO:14; (c) a RNA comprising an antisense sequence set forth in SEQ ID NO:9 and a sense sequence set forth in SEQ ID NO:10 and a RNA comprising an antisense sequence set forth in SEQ ID NO:15 and a sense sequence set forth in SEQ ID NO:16; (d) a RNA comprising an antisense sequence set forth in SEQ ID NO:9 and a sense sequence set forth in SEQ ID NO:10 and a RNA comprising an antisense sequence set forth in SEQ ID NO:19 and a sense sequence set forth in SEQ ID NO:20; (e) a RNA comprising an antisense sequence set forth in SEQ ID NO:9 and a sense sequence set forth in SEQ ID NO:10 and a RNA comprising an antisense sequence set forth in SEQ ID NO:21 and a sense sequence set forth in SEQ ID NO:22; (f) a RNA comprising an antisense sequence set forth in SEQ ID NO:9 and a sense sequence set forth in SEQ ID NO:10 and a RNA comprising an antisense sequence set forth in SEQ ID NO:23 and a sense sequence set forth in SEQ ID NO:24; (g) a RNA comprising an antisense sequence set forth in SEQ ID NO:11 and a sense sequence set forth in SEQ ID NO:12 and a RNA comprising an antisense sequence set forth in SEQ ID NO:13 and a sense sequence set forth in SEQ ID NO:14; (h) a RNA comprising an antisense sequence set forth in SEQ ID NO:11 and a sense sequence set forth in SEQ ID NO:12 and a RNA comprising an antisense sequence set forth in SEQ ID NO:15 and a sense sequence set forth in SEQ ID NO:16; (i) a RNA comprising an antisense sequence set forth in SEQ ID NO:11 and a sense sequence set forth in SEQ ID NO:12 and a RNA comprising an antisense sequence set forth in SEQ ID NO:19 and a sense sequence set forth in SEQ ID NO:20; (j) a RNA comprising an antisense sequence set forth in SEQ ID NO:11 and a sense sequence set forth in SEQ ID NO:12 and a RNA comprising an antisense sequence set forth in SEQ ID NO:21 and a sense sequence set forth in SEQ ID NO:22; (k) a RNA comprising an antisense sequence set forth in SEQ ID NO:11 and a sense sequence set forth in SEQ ID NO:12 and a RNA comprising an antisense sequence set forth in SEQ ID NO:23 and a sense sequence set forth in SEQ ID NO:24; (l) a RNA comprising an antisense sequence set forth in SEQ ID NO:13 and a sense sequence set forth in SEQ ID NO:14 and a RNA comprising an antisense sequence set forth in SEQ ID NO:15 and a sense sequence set forth in SEQ ID NO:16; (m) a RNA compmrising an antisense sequence set forth in SEQ ID NO:13 and a sense sequence set forth in SEQ ID NO:14 and a RNA comprising an antisense sequence set forth in SEQ ID NO:19 and a sense sequence set forth in SEQ ID NO:20; (n) a RNA comprising an antisense sequence set forth in SEQ ID NO:13 and a sense sequence set forth in SEQ ID NO:14 and a RNA comprising an antisense sequence set forth in SEQ ID NO:21 and a sense sequence set forth in SEQ ID NO:22; (o) a RNA comprising an antisense sequence set forth in SEQ ID NO:13 and a sense sequence set forth in SEQ ID NO:14 and a RNA comprising an antisense sequence set forth in SEQ ID NO:23 and a sense sequence set forth in SEQ ID NO:24; (p) a RNA comprising an antisense sequence set forth in SEQ ID NO:15 and a sense sequence set forth in SEQ ID NO:16 and a RNA comprising an antisense sequence set forth in SEQ ID NO:17 and a sense sequence set forth in SEQ ID NO: 18; (q) a RNA comprising an antisense sequence set forth in SEQ ID NO:15 and a sense sequence set forth in SEQ ID NO:16 and a RNA comprising an antisense sequence set forth in SEQ ID NO:19 and a sense sequence set forth in SEQ ID NO:20; (r) a RNA comprising an antisense sequence set forth in SEQ ID NO:15 and a sense sequence set forth in SEQ ID NO:16 and a RNA comprising an antisense sequence set forth in SEQ ID NO:21 and a sense sequence set forth in SEQ ID NO:22 (s) a RNA comprising an antisense sequence set forth in SEQ ID NO:15 and a sense sequence set forth in SEQ ID NO:16 and a RNA comprising an antisense sequence set forth in SEQ ID NO:23 and a sense sequence set forth in SEQ ID NO:24; (t) a RNA comprising an antisense sequence set forth in SEQ ID NO:17 and a sense sequence set forth in SEQ ID NO: 18 and a RNA comprising an antisense sequence set forth in SEQ ID NO:19 and a sense sequence set forth in SEQ ID NO:20; (u) a RNA comprising an antisense sequence set forth in SEQ ID NO:17 and a sense sequence set forth in SEQ ID NO: 18 and a RNA comprising an antisense sequence set forth in SEQ ID NO:21 and a sense sequence set forth in SEQ ID NO:22 (v) a RNA comprising an antisense sequence set forth in SEQ ID NO:17 and a sense sequence set forth in SEQ ID NO: 18 and a RNA comprising an antisense sequence set forth in SEQ ID NO:23 and a sense sequence set forth in SEQ ID NO:24 (w) a RNA comprising an antisense sequence set forth in SEQ ID NO:19 and a sense sequence set forth in SEQ ID NO:20 and a RNA comprising an antisense sequence set forth in SEQ ID NO:21 and a sense sequence set forth in SEQ ID NO:22; (x) a RNA comprising an antisense sequence set forth in SEQ ID NO:19 and a sense sequence set forth in SEQ ID NO:20 and a RNA comprising an antisense sequence set forth in SEQ ID NO:23 and a sense sequence set forth in SEQ ID NO:24; and (y) a RNA comprising an antisense sequence set forth in SEQ ID NO:21 and a sense sequence set forth in SEQ ID NO:22 and a RNA comprising an antisense sequence set forth in SEQ ID NO:23 and a sense sequence set forth in SEQ ID NO:24. In one example, the plurality of RNAs comprises at least one RNA selected from the group consisting of: (a) a RNA comprising an antisense sequence set forth in SEQ ID NO:9 and a sense sequence set forth in SEQ ID NO:10 and a RNA comprising an antisense sequence set forth in SEQ ID NO:23 and a sense sequence set forth in SEQ ID NO:24; (b) a RNA comprising an antisense sequence set forth in SEQ ID NO:13 and a sense sequence set forth in SEQ ID NO:14 and a RNA comprising an antisense sequence set forth in SEQ ID NO:23 and a sense sequence set forth in SEQ ID NO:24; (c) a RNA comprising an antisense sequence set forth in SEQ ID NO:15 and a sense sequence set forth in SEQ ID NO:16 and a RNA comprising an antisense sequence set forth in SEQ ID NO:23 and a sense sequence set forth in SEQ ID NO:24; (d) a RNA comprising an antisense sequence set forth in SEQ ID NO:17 and a sense sequence set forth in SEQ ID NO: 18 and a RNA comprising an antisense sequence set forth in SEQ ID NO:23 and a sense sequence set forth in SEQ ID NO:24; (e) a RNA comprising an antisense sequence set forth in SEQ ID NO:19 and a sense sequence set forth in SEQ ID NO:20 and a RNA comprising an antisense sequence set forth in SEQ ID NO:23 and a sense sequence set forth in SEQ ID NO:24; (f) a RNA comprising an antisense sequence set forth in SEQ ID NO:15 and a sense sequence set forth in SEQ ID NO:16 and a RNA comprising an antisense sequence set forth in SEQ ID NO:19 and a sense sequence set forth in SEQ ID NO:20; (g) a RNA comprising an antisense sequence set forth in SEQ ID NO:9 and a sense sequence set forth in SEQ ID NO:10 and a RNA comprising an antisense sequence set forth in SEQ ID NO:21 and a sense sequence set forth in SEQ ID NO:22; (h) a RNA comprising an antisense sequence set forth in SEQ ID NO:11 and a sense sequence set forth in SEQ ID NO:12 and a RNA comprising an antisense sequence set forth in SEQ ID NO:21 and a sense sequence set forth in SEQ ID NO:22; (i) a RNA comprising an antisense sequence set forth in SEQ ID NO:13 and a sense sequence set forth in SEQ ID NO:14 and a RNA comprising an antisense sequence set forth in SEQ ID NO:21 and a sense sequence set forth in SEQ ID NO:22; (j) a RNA comprising an antisense sequence set forth in SEQ ID NO:15 and a sense sequence set forth in SEQ ID NO:16 and a RNA comprising an antisense sequence set forth in SEQ ID NO:21 and a sense sequence set forth in SEQ ID NO:22; (k) a RNA comprising an antisense sequence set forth in SEQ ID NO:17 and a sense sequence set forth in SEQ ID NO: 18 and a RNA comprising an antisense sequence set forth in SEQ ID NO:21 and a sense sequence set forth in SEQ ID NO:22; (l) a RNA comprising an antisense sequence set forth in SEQ ID NO:19 and a sense sequence set forth in SEQ ID NO:20 and a RNA comprising an antisense sequence set forth in SEQ ID NO:21 and a sense sequence set forth in SEQ ID NO:22; (m) a RNA comprising an antisense sequence set forth in SEQ ID NO:21 and a sense sequence set forth in SEQ ID NO:22 and a RNA comprising an antisense sequence set forth in SEQ ID NO:23 and a sense sequence set forth in SEQ ID NO:24. In one example, the plurality of RNAs of claim 3 or claim 4, comprising a RNA comprising an antisense sequence set forth in SEQ ID NO:15 and a sense sequence set forth in SEQ ID NO:16 and a RNA comprising an antisense sequence set forth in SEQ ID NO:19 and a sense sequence set forth in SEQ ID NO:20. In one example, the plurality of RNAs described herein are provided in a single composition. In another example, the plurality of RNAs described herein are provided as multiple compositions. For example, each of the RNAs of the plurality may be provided separately. Alternatively, at least one RNA of the plurality may be provided separately and two or more of the plurality provided together in a composition. At least one or each of the RNAs in the plurality of RNAs described herein may be present in the form of a siRNA. For example, the present disclosure may provide a plurality of siRNAs. The nucleic acid in accordance with the present disclosure may comprise, or be in operable linkage with, one or more transcriptional terminator sequences. For example, the nucleic acid may comprise a transcriptional terminator sequence at the 3’ terminus of the sequence encoding the RNA. Such sequences will be known to a person of skill in the art, but may include ‘TTTTT’ or ‘TTTTTT’. Alternatively, or in addition, the nucleic acid in accordance with the present disclosure may comprise, or be in operable linkage with, transcription initiator sequence. For example, the nucleic acid may comprise a transcription initiator sequence at the 5’ terminus of the sequence encoding the RNA. Such sequences will be known to a person of skill in the art, but may include ‘G’. Alternatively, or in addition, the nucleic acid in accordance with the present disclosure may comprise one or more restriction sites e.g., to facilitate cloning of the nucleic acid(s) into cloning or expression vectors. For example, the nucleic acids described herein may include a restriction site upstream and/or downstream of the sequence encoding a RNA of the disclosure. Suitable restriction enzyme recognition sequences will be known to a person of skill in the art. However, in one example, the nucleic acid(s) of the disclosure may include a BamH1 restriction site (GGATCC) at the 5’ terminus i.e., upstream of the sequence encoding the RNA, and a EcoR1 restriction site (GAATTC) at the 3’ terminus i.e., downstream of the sequence encoding the RNA. The present disclosure also provides a method of treating or preventing SARS-CoV-2 infection in a subject, the method comprising administering a therapeutically effective amount of a RNA, plurality of RNAs, nucleic acid, expression vector and/or composition described herein. The present disclosure also provides a method of reducing SARS-CoV-2 viral load in a subject infected with SARS-CoV-2, the method comprising administering a therapeutically effective amount of a RNA, plurality of RNAs, nucleic acid, expression vector and/or composition described herein. The present disclosure also provides a method of reducing severity of one or more symptoms associated with SARS-CoV-2 infection in a subject, the method comprising administering to the subject a therapeutically effective amount of a RNA, plurality of RNAs, nucleic acid, expression vector and/or composition described herein. The present disclosure also provides a method of reducing the infectivity of SARS-CoV-2 in a subject infected with SARS-CoV-2, the method comprising administering to the subject a therapeutically effective amount of a RNA, plurality of RNAs, nucleic acid, expression vector and/or composition described herein. A method of reducing the likelihood of long COVID in a subject infected SARS-CoV-2, comprising administering to the subject a therapeutically effective amount of a RNA, plurality of RNAs, nucleic acid, expression vector and/or composition described herein. In accordance with any method described herein, in one example, the subject is receiving simultaneous treatment for SARS-CoV-2 infection. Alternatively, the subject is receiving separate treatment for SARS-CoV-2 infection. In another example, the subject is receiving sequential treatment for SARS-CoV-2infection. In accordance with any method described herein, in one example, the subject has not had a previous SARS-CoV-2 infection. Alternatively, the subject has had a previous SARS-CoV-2 infection. In one example, the methods described herein comprise inhibiting expression of one or more transcripts encoded by the SARS-CoV-2 genome in the subject. In another example, the medicament described herein inhibits expression of one or more SARS-CoV-2 genes. In one example, the subject to which the RNA, plurality of RNAs, nucleic acid, expression vector, and/or composition of the disclosure is/are administered is receiving treatment with another therapeutic agent for treating SARS-CoV-2 infection. In another example, the subject to which the RNA, plurality of RNAs, nucleic acid, expression vector, and/or composition of the disclosure is/are administered has already received treatment with another therapeutic agent for treating SARS-CoV-2 infection. For example, the subject and/or the SARS-CoV-2 is refractory or resistant to treatment with the other agent known for treating SARS-CoV-2 infection. In another example, the subject to which the RNA, plurality of RNAs, nucleic acid, expression vector, and/or composition of the disclosure is/are administered has not yet received treatment with another therapeutic agent for treating SARS-CoV-2 infection. In another example, the RNA, plurality of RNAs, nucleic acid, expression vector, and/or composition of the disclosure is administered in combination with another therapeutic agent known for treating SARS-CoV-2 infection i.e., as an adjunctive therapy. In one example, a composition of the present disclosure is provided in a kit. For example, a composition of the present disclosure is packaged together with one or more other therapeutic agents known for treating SARS-CoV-2 infections. Such other therapeutic agents will be known to a person of skill in the art. In another example, the composition is packaged with instruction for use in a method of the disclosure. The present disclosure also provides use of a RNA, plurality of RNAs, nucleic acid, expression vector and/or composition described herein in the preparation of a medicament, e.g., for treating SARS-CoV-2 infection in a subject and/or in a method disclosed herein. The present disclosure also provides a RNA, plurality of RNAs, nucleic acid, expression vector and/or composition described herein for use in therapy. For example, the RNA, plurality of RNAs, nucleic acid, expression vector and/or composition may be for use in treating SARS- CoV-2 infection in a subject and/or in a method disclosed herein. Treatment of SARS-CoV-2 in accordance with any example described herein, may comprise one or more of reducing SARS-CoV-2 viral load in the subject, reducing severity of symptoms associated with SARS-CoV-2 infection, reducing the likelihood of long COVID and/or reducing the infectivity of SARS-CoV-2 in a subject. In one example, the medicament will reduce SARS-CoV-2 gene transcription products in the subject to which the medicament is administered. Brief Description of Drawings Figure 1 shows the results of the siRNA panel screen against SARS-CoV-2. (a) HEKAT10 cells were treated with 5 nM siRNA, 1 hour prior to addition of SARS-CoV-2, isolate VIC01. Cells were stained with NucBlue™ and imaged using the IN Cell Analyzer 72 hours post- infection. Total culture populations were counted using IN Carta Image Analysis Software and were normalized to uninfected control populations. Statistical comparisons were made between infected siRNA-control populations and therapeutic siRNA treated cultures using a One-Way ANOVA. Data is the mean ±SEM of 6 replicates and significance shown is: **=P<0.01, ***=P<0.001, ****=P<0.0001. (b) IN Cell Analyzer images of NucBlue™ stained HEKAT10 cells treated with siRNA 72 hours post-infection. Figure 2 illustrates the results from screening the most promising siRNA against SARS- CoV-2 variants. The 16 most promising siRNA were screened against SARS-CoV-2 variants, using HEKAT10 cells. Cells were treated with 5 nM siRNA, 1 hour prior to SARS-CoV-2 (a) Alpha, (b) Beta, (c) Gamma, (d) Delta, (e) Zeta and (f) Kappa challenge. Cells were stained with NucBlue™ and imaged using the IN Cell Analyzer 72 hours post-infection. Total culture populations were counted using IN Carta Image Analysis Software and cell survival data was normalized to uninfected control populations. Statistical comparisons were made between infected siRNA-control populations and therapeutic siRNA treated cultures using a One-Way ANOVA. Data is the mean ±SEM of 6 replicates and significance shown is: *=P<0.05, **=P<0.01, ***=P<0.001, ****=P<0.0001. Figure 3 illustrates the impact of siRNA treatments on SARS-CoV-2 viral load and viral protein. HEKAT10 cells were transfected with 5 nM of siRNA, 1 hour prior to SARS-CoV-2 (a) Beta and (b) Delta challenge. Cell culture supernatant of the top eight siRNA was measured for SARS-CoV-2 Nucleocapsid RNA via RT-qPCR 72 hours post-infection. Statistical comparisons were made between infected siRNA-control populations and therapeutic siRNA treated cultures using a One-Way ANOVA. Data is the mean ±SEM of 6 replicates. (c) HEKAT10 cells were transfected with 5 nM of the top 8 siRNA, 1 hour prior to SARS-CoV-2 Beta challenge and cell lysates were harvested 72 hours post-infection. Untreated infected control was harvested 48 hours post-infection. SDS-PAGE was performed, and samples were immunoblotted for SARS- CoV-2 Nucleocapsid protein and GAPDH. Immunoblots were visualized with G:BOX Chemi XX6 and GeneSys image acquisition software. (d) Quantification of immunoblots was completed with ImageJ and densitometry was normalized to GAPDH. Data was made relative to infected siRNA-control populations, and statistical comparisons were made between infected siRNA-control cultures and therapeutic siRNA treated cultures using an unpaired t test. Data is the mean ±SEM of 3 replicates. Significance shown is: *=P<0.05, **=P<0.01, ***=P<0.001, ****=P<0.0001. Figure 4 shows the effects of the expression of the siRNA in the Vero E6 cell line infected with SARS-CoV-2 variants of concern. Vero E6 cells were transfected with 5 nM of the 8 more effective siRNA, 1 hour prior to SARS-CoV-2 (a, b) Beta, (c, d) Delta and (e, f) Omicron strain infection. (a, c, e) Cells were stained with NucBlue™ and imaged using the IN Cell Analyzer 72 hours post-infection. Total culture populations were counted using IN Carta Image Analysis Software and cell survival data was normalized to uninfected control populations. (b, d, f) Cell culture supernatant was collected 72 hours post-infection and measured for SARS-CoV-2 Nucleocapsid RNA via RT-qPCR. Statistical comparisons of both data sets were made between infected siRNA-control populations and therapeutic siRNA treated cultures using a One-Way ANOVA. Data is the mean ±SEM of 6 replicates and significance shown is: *=P<0.05, **=P<0.01, ***=P<0.001, ****=P<0.0001. Figure 5 shows the antiviral effectiveness of multiplexed siRNAs. Vero E6 cells were co- transfected with each pair combination of the lead eight siRNAs (5 nM total), 1 hour prior to SARS-CoV-2 Delta challenge. (a) Cells were stained with NucBlue™ and imaged using the IN Cell Analyzer 72 hours post-infection. Total culture populations were counted using IN Carta Image Analysis Software and cell survival data was normalized to uninfected control populations. (b) Cell culture supernatant was collected 72 hours post-infection and measured for SARS-CoV-2 Nucleocapsid RNA via RT-qPCR. Statistical comparisons of both data sets were made between infected siRNA-control populations and therapeutic siRNA treated cultures using a One-Way ANOVA. Data is the mean ±SEM of 6 replicates and significance shown is: ****=P<0.0001. Figure 6 shows the comparison of the siRNA against clinically approved drugs. Vero E6 cells were transfected with 5 nM of siRNAs 18, 27 or 30 or with Remdesivir (RDV) or Sotrovimab (STV) at their previously reported IC50 and 5X IC50 concentrations (18-20), 1 hour prior to SARS-CoV-2 Delta infection. (a) Cells were stained with NucBlue™ and imaged using the IN Cell Analyzer 72 hours post-infection. Total culture populations were counted using IN Carta Image Analysis Software and cell survival data was normalized to uninfected control populations. (b) Cell culture supernatant was collected 72 hours post-infection and measured for SARS-CoV-2 Nucleocapsid RNA via RT-qPCR. Statistical comparisons of both data sets were made between infected siRNA-control populations and therapeutic siRNA treated cultures using a One-Way ANOVA. Data is the mean ±SEM of six replicates and significance shown is: *=P<0.05, **=P<0.01, ***=P<0.001, ****=P<0.0001. (RDV IC50 = 1 µM, 5X IC50 = 5 µM; SDV IC₅₀ = 372 ng/mL, 5X IC₅₀ = 1860 ng/mL). Figure 7 shows the results of the siRNA screen for off-target effects. Vero E6 cells were transfected with 5 nM of the top siRNA.72 hours post-transfection, cellular RNA was harvested and measured for three type I interferon-stimulated genes, (a) ISG20, (b) Viperin and (c) IFIT1. mRNA was detected via RT qPCR and normalized to Mock transfected populations. Statistical comparisons were made between siRNA-control populations and therapeutic siRNA treated cultures using a One-Way ANOVA. The positive control IFNβ was not included in the statistical comparisons. Data is the mean ±SEM of 6 replicates and significance shown is: *=P<0.05, **=P<0.01, ***=P<0.001, ****=P<0.0001. Figure 8 shows the conservation of siRNA sequences throughout SARS-CoV-2 variants. (a) Relative locations of the top siRNAs designed to target various regions of SARS-CoV-2 are indicated along the genome. siRNAs 2 and 7 target the 5’UTR, 27 and 30 target NSP1 produced from the ORF1ab polyprotein, and 16, 21, 18 and 25 target the Spike, Envelope, Membrane and Nucleocapsid regions, respectively. (b) Publicly available SARS-CoV-2 sequences were assessed for complete conservation of siRNA target sites. Horizontal bars indicate that the siRNA target site was conserved in its entirety of the percentage of sequences analyzed, i.e., complete conservation of target site across all analyzed sequences yielded a result of 100% conserved. Figure 9 shows the expression of GFP in 293T reporter cell-lines expressing GFP fused SARS-CoV-2 proteins after transfection with Lipid nanoparticle (LNP)-siRNAs. (A) SARS- CoV-2 Mem-GFP expression after transfection with 50 nM of LNP-siRNA18 (red), and Lipofectamine-siRNA18 (blue) in reporter cell line with FG11F-Lentiviral vectors encoding GFP fused SARS-CoV-2-Membrane protein. (B) LNP rate of delivery with 50 nM of LNP- siRNA18 (red), and Lipofectamine-siRNA18 (blue) in GFP fused SARS-CoV-2-Membrane protein reporter cell line. (C) SARS-CoV-2 Nuc-GFP expression after transfection 50 nM of LNP-siRNA25 (red), and Lipofectamine-siRNA25 (blue) in a reporter cell line with FG11F- Lentiviral vectors encoding GFP fused SARS-CoV-2-Nucleoprotein. (D) LNP rate of delivery with 50 nM of LNP-siRNA25 (red), and Lipofectamine-siRNA25 (blue) in GFP fused SARS- CoV-2-Nucleoprotein reporter cell line. The Lipofectamine-siRNA complexes were not fluorescently labelled. Figure 10 shows that antiviral siRNAs complexed to LNPs are successfully delivered to Vero E6 cells and can functionally silence SARS-CoV-2 strain Omicron BA.1 in a virus challenge. Cell survival was assessed at Day 3 (left panel) and Day 4 (right panel) and all uninfected cultures (No CoV) and all infected LNP-siRNA treatments showed significant cell survival compared to the infected control culture (Ctrl – CoV) (p <0.0001). Ordinary one-way ANOVA, Dunnett’s multiple comparisons test. Figure 11 shows that antiviral siRNAs complexed to LNPs are successfully delivered to Vero E6 cells and can functionally silence SARS-CoV-2 strain Omicron BA.1 in a virus challenge. NC viral RNA levels were measured at Day 3 (left panel) and Day 4 (right panel) post infection and show significant reduction in viral RNA in all LNP-siRNA27 or LNP-siRNA30 treated cultures, as well as LNP-siRNA27 and siRNA30 combinations, compared to the infected control with no siRNA treatment (Pos Ctrl). Ordinary one-way ANOVA, **** p <0.0001. Key to the Sequence Listing SEQ ID NO: 1: RNA sequence for target region within SARS-CoV-2 genome designated Region 1. SEQ ID NO: 2: RNA sequence for target region within SARS-CoV-2 genome designated Region 2. SEQ ID NO: 3: RNA sequence for target region within SARS-CoV-2 genome designated Region 3. SEQ ID NO: 4: RNA sequence for target region within SARS-CoV-2 genome designated Region 4. SEQ ID NO: 5: RNA sequence for target region within SARS-CoV-2 genome designated Region 5. SEQ ID NO: 6: RNA sequence for target region within SARS-CoV-2 genome designated Region 6. SEQ ID NO: 7: RNA sequence for target region within SARS-CoV-2 genome designated Region 7. SEQ ID NO: 8: RNA sequence for target region within SARS-CoV-2 genome designated Region 8. SEQ ID NO: 9: RNA antisense sequence for siRNA designated siRNA 2. SEQ ID NO: 10: RNA sense sequence for siRNA designated siRNA 2. SEQ ID NO: 11: RNA antisense sequence for siRNA designated siRNA 7. SEQ ID NO: 12: RNA sense sequence for siRNA designated siRNA 7. SEQ ID NO: 13: RNA antisense sequence for siRNA designated siRNA 16. SEQ ID NO: 14: RNA sense sequence for siRNA designated siRNA16. SEQ ID NO: 15: RNA antisense sequence for siRNA designated siRNA18. SEQ ID NO: 16: RNA sense sequence for siRNA designated siRNA18. SEQ ID NO: 17: RNA antisense sequence for siRNA designated siRNA21. SEQ ID NO: 18: RNA sense sequence for siRNA designated siRNA21. SEQ ID NO: 19: RNA antisense sequence for siRNA designated siRNA25. SEQ ID NO: 20: RNA sense sequence for siRNA designated siRNA25. SEQ ID NO: 21: RNA antisense sequence for siRNA designated siRNA27. SEQ ID NO: 22: RNAsense sequence for siRNA designated siRNA27. SEQ ID NO: 23: RNA antisense sequence for siRNA designated siRNA30. SEQ ID NO: 24: RNA sense sequence for siRNA designated siRNA30. SEQ ID NO: 25: siRNA control antisense sequence SEQ ID NO: 26: siRNA control sense sequence SEQ ID NO: 27: Nucleocapsid forward primer SEQ ID NO: 28: Nucleocapsid reverse primer SEQ ID NO: 29: Nucleocapsid probe sequence SEQ ID NO: 30: ISG20 forward primer SEQ ID NO: 31: ISG20 reverse primer SEQ ID NO: 32: Viperin forward primer SEQ ID NO: 33: Viperin reverse primer SEQ ID NO: 34: IFIT1 forward primer SEQ ID NO: 35: IFIT1 reverse primer SEQ ID NO: 36: GADPH forward primer SEQ ID NO: 37: GADPH reverse primer SEQ ID NO: 38: RNA sequence of exemplary SARS-CoV-2 genome (Genbank Accession no. MT007544) SEQ ID NO: 39: RNA antisense sequence for siRNA designated siRNA 2 (no overhang) SEQ ID NO: 40: RNA sense sequence for siRNA designated siRNA 2 (no overhang) SEQ ID NO: 41: RNA antisense sequence for siRNA designated siRNA 7 (no overhang) SEQ ID NO: 42: RNA sense sequence for siRNA designated siRNA 7 (no overhang) SEQ ID NO: 43: RNA antisense sequence for siRNA designated siRNA 46 (no overhang) SEQ ID NO: 44: RNA sense sequence for siRNA designated siRNA46 (no overhang) SEQ ID NO: 45: RNA antisense sequence for siRNA designated siRNA48 (no overhang) SEQ ID NO: 46: RNA sense sequence for siRNA designated siRNA48 (no overhang) SEQ ID NO: 47: RNA antisense sequence for siRNA designated siRNA24 (no overhang) SEQ ID NO: 48: RNA sense sequence for siRNA designated siRNA24 (no overhang) SEQ ID NO: 49: RNA antisense sequence for siRNA designated siRNA25 (no overhang) SEQ ID NO: 50: RNA sense sequence for siRNA designated siRNA25 (no overhang) SEQ ID NO: 51: RNA antisense sequence for siRNA designated siRNA27 (no overhang) SEQ ID NO: 52: RNA sense sequence for siRNA designated siRNA27 (no overhang) SEQ ID NO: 53: RNA antisense sequence for siRNA designated siRNA30 (no overhang) SEQ ID NO: 54: RNA sense sequence for siRNA designated siRNA30 (no overhang) SEQ ID NO: 55: siRNA control antisense sequence (no overhang) SEQ ID NO: 56: siRNA control sense sequence (no overhang) SEQ ID NO: 57: siRNA control antisense sequence SEQ ID NO: 58: siRNA control sense sequence Detailed Description General Throughout this specification, unless specifically stated otherwise or the context requires otherwise, reference to a single step, feature, composition of matter, group of steps or group of features or compositions of matter shall be taken to encompass one and a plurality (i.e. one or more) of those steps, features, compositions of matter, groups of steps or groups of features or compositions of matter. Those skilled in the art will appreciate that the present disclosure is susceptible to variations and modifications other than those specifically described. It is to be understood that the disclosure includes all such variations and modifications. The disclosure also includes all of the steps, features, compositions and compounds referred to or indicated in this specification, individually or collectively, and any and all combinations or any two or more of said steps or features. The present disclosure is not to be limited in scope by the specific examples described herein, which are intended for the purpose of exemplification only. Functionally-equivalent products, compositions and methods are clearly within the scope of the present disclosure. Any example of the present disclosure herein shall be taken to apply mutatis mutandis to any other example of the disclosure unless specifically stated otherwise. Unless specifically defined otherwise, all technical and scientific terms used herein shall be taken to have the same meaning as commonly understood by one of ordinary skill in the art (for example, in cell culture, molecular genetics, immunology, immunohistochemistry, protein chemistry, and biochemistry). Unless otherwise indicated, the recombinant DNA, recombinant protein, cell culture, and immunological techniques utilized in the present disclosure are standard procedures, well known to those skilled in the art. Such techniques are described and explained throughout the literature in sources such as, J. Perbal, A Practical Guide to Molecular Cloning, John Wiley and Sons (1984), J. Sambrook et al. Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press (1989), T.A. Brown (editor), Essential Molecular Biology: A Practical Approach, Volumes 1 and 2, IRL Press (1991), D.M. Glover and B.D. Hames (editors), DNA Cloning: A Practical Approach, Volumes 1-4, IRL Press (1995 and 1996), and F.M. Ausubel et al. (editors), Current Protocols in Molecular Biology, Greene Pub. Associates and Wiley- Interscience (1988, including all updates until present), Ed Harlow and David Lane (editors) Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, (1988), and J.E. Coligan et al. (editors) Current Protocols in Immunology, John Wiley & Sons (including all updates until present). Throughout this specification, unless the context requires otherwise, the word "comprise", or variations such as "comprises" or "comprising", is understood to imply the inclusion of a stated step or element or integer or group of steps or elements or integers but not the exclusion of any other step or element or integer or group of elements or integers. The term “and/or”, e.g., “X and/or Y” shall be understood to mean either “X and Y” or “X or Y” and shall be taken to provide explicit support for both meanings or for either meaning. Selected Definitions By "RNA" is meant a molecule comprising at least one ribonucleotide residue. By "ribonucleotide" is meant a nucleotide with a hydroxyl group at the 2' position of a β-D-ribo- furanose moiety. The terms include double-stranded RNA, single-stranded RNA, isolated RNA such as partially purified RNA, essentially pure RNA, synthetic RNA, recombinantly produced RNA, as well as altered RNA that differs from naturally occurring RNA by the addition, deletion, substitution and/or alteration of one or more nucleotides. Such alterations can include addition of non-nucleotide material, such as to the end(s) of the siRNA or internally, for example at one or more nucleotides of the RNA. Nucleotides in the RNA molecules of the instant disclosure can also comprise non-standard nucleotides, such as non-naturally occurring nucleotides or chemically synthesized nucleotides or deoxynucleotides. These altered RNAs can be referred to as analogs or analogs of naturally-occurring RNA. In one example, all of the residues in the RNA are ribonucleotides. As used herein, the term “RNAi reagent” refers to a RNA that is capable of eliciting "RNA interference" or "RNAi". The term "RNA interference" or "RNAi" refers generally to RNA-dependent silencing of gene expression initiated by double stranded RNA (dsRNA) molecules in a cell's cytoplasm. The dsRNA molecule reduces or inhibits transcription products of a target nucleic acid sequence, thereby silencing the gene. As used herein, the term "double stranded RNA" or "dsRNA" refers to a RNA molecule having a duplex structure and comprising an antisense sequence and a sense sequence which are of similar length to one another. The antisense sequence and the sense sequence can be in a single RNA strand or in separate RNA strands. The "antisense sequence" (often referred to as a “guide strand”) is substantially complementary to a target sequence, which in the present case, is a region of a RNA transcription product of the SARS-CoV-2 genome. The “target sequence” may be a region of the SARS-CoV-2 genome which is highly conserved across all variants. The genome sequence of SARS-CoV-2 is publicly available. An exemplary sequence is provided in SEQ ID NO: 38. The “antisense sequence” can also be referred to as the “effector sequence”. The “sense sequence” will be of sufficient complementary to the antisense sequence such that it can anneal to the antisense sequence to form a duplex. In this regard, the sense sequence will be substantially homologous to a region of target sequence. As will be apparent to the skilled person, the term “sense sequence” can also be referred to as the “complement of the antisense sequence” or the sense sequence. As used herein, the term "duplex” refers to regions in two complementary or substantially complementary nucleic acids (e.g., RNAs), or in two complementary or substantially complementary regions of a single-stranded nucleic acid (e.g., RNA), that form base pairs with one another, either by Watson-Crick base pairing or any other manner that allows for a stabilized duplex between the nucleotide sequences that are complementary or substantially complementary. It will be understood by the skilled person that within a duplex region, 100% complementarity is not required; substantial complementarity is allowable. Substantial complementarity may include 95% or greater complementarity. For example, a single mismatch in a duplex region consisting of 19 base pairs (i.e., 18 base pairs and one mismatch) results in 95% complementarity, rendering the duplex region substantially complementary. In another example, two mismatches in a duplex region consisting of 19 base pairs (i.e., 17 base pairs and two mismatches) results in 89.5% complementarity, rendering the duplex region substantially complementary. In yet another example, three mismatches in a duplex region consisting of 19 base pairs (i.e., 16 base pairs and three mismatches) results in 84.2% complementarity, rendering the duplex region substantially complementary, and so on. The dsRNA may be provided as a hairpin or stem loop structure, with a duplex region comprised of an antisense sequence and sense sequence linked by at least 2 nucleotide sequence which is termed a stem loop. When a dsRNA is provided as a hairpin or stem loop structure it can be referred to as a "hairpin RNA" or "short hairpin RNAi agent" or "shRNA". As used herein, the term “complementary” with regard to a sequence refers to a complement of the sequence by Watson-Crick base pairing, whereby guanine (G) pairs with cytosine (C), and adenine (A) pairs with either uracil (U) or thymine (T). A sequence may be complementary to the entire length of another sequence, or it may be complementary to a specified portion or length of another sequence. One of skill in the art will recognize that U may be present in RNA, and that T may be present in DNA. Therefore, an A within either of a RNA or DNA sequence may pair with a U in a RNA sequence or T in a DNA sequence. As used herein, the term "substantially complementary" is used to indicate a sufficient degree of complementarity or precise pairing such that stable and specific binding occurs between nucleic acid sequences e.g., between the antisense sequence and the sense sequence or between the antisense sequence and the target sequence. It is understood that the sequence of a nucleic acid need not be 100% complementary to that of its target or complement. The term encompasses a sequence complementary to another sequence with the exception of an overhang. In some cases, the sequence is complementary to the other sequence with the exception of 1-2 mismatches. In some cases, the sequences are complementary except for 1 mismatch. In some cases, the sequences are complementary except for 2 mismatches. In other cases, the sequences are complementary except for 3 mismatches. The term “encoded”, as used in the context of a RNA of the disclosure, shall be understood to mean a RNA is capable of being transcribed from a DNA template. Accordingly, a nucleic acid that encodes a RNA of the disclosure will comprise a DNA sequence which serves as a template for transcription of the respective RNA. A “vector” will be understood to mean a vehicle for introducing a nucleic acid into a cell. Vectors include, but are not limited to, plasmids, phagemids, viruses, bacteria, and vehicles derived from viral or bacterial sources. A “plasmid” is a circular, double-stranded DNA molecule. A useful type of vector for use in accordance with the present disclosure is a viral vector, wherein heterologous DNA sequences are inserted into a viral genome that can be modified to delete one or more viral genes or parts thereof. Certain vectors are capable of autonomous replication in a host cell (e.g., vectors having an origin of replication that functions in the host cell). Other vectors can be stably integrated into the genome of a host cell, and are thereby replicated along with the host genome. As used herein, the term "expression vector" will be understood to mean a vector capable of expressing a RNA molecule of the disclosure. As used herein, the terms "treating", "treat" or "treatment" and variations thereof, refer to clinical intervention designed to alter the natural course of the individual or cell being treated during the course of clinical pathology. Desirable effects of treatment include decreasing the rate of disease progression, ameliorating or palliating the disease state, and remission or improved prognosis. It follows that treatment of SARS-CoV-2 infection includes reducing SARS-CoV-2 viral load in a subject infected with SARS-CoV-2, reducing severity of symptoms associated with SARS-CoV-2 infection, reducing the likelihood of long COVID in a subject and reducing the infectivity of SARS-CoV-2 in a subject. An individual is successfully "treated", for example, if one or more of the above treatment outcomes is achieved. The terms “prevent”, “preventing” and “prevention” refer to the prevention of the onset, recurrence or spread of a disease, disorder or condition, or of one or more symptoms thereof. For example, the terms refer to the treatment with or administration of a RNA molecule of the disclosure prior to the onset of symptoms, particularly to subjects at risk of a disease, disorder or condition described herein. The terms encompass the inhibition or reduction of a symptom of the particular disease, disorder or conditions. In addition, subjects who have a history of recurring symptoms are also potential candidates for prevention. In this regard, the term “prevention” may be interchangeably used with the term “prophylactic treatment”. A "therapeutically effective amount" is at least the minimum concentration or amount required to effect a measurable improvement of a particular disease (e.g., a SARS-CoV-2 infection). A therapeutically effective amount herein may vary according to factors such as the disease state, age, sex, and weight of the patient, and the ability of the RNA or expression construct to elicit a desired response in the individual. A therapeutically effective amount is also one in which any toxic or detrimental effects of the RNA, or expression construct are outweighed by the therapeutically beneficial effects. As used herein, the “subject” or “patient” can be a human or non-human animal infected with SARS-CoV-2. The “non-human animal” may be a primate, livestock (e.g. sheep, horses, cattle, pigs, donkeys), companion animal (e.g. pets such as dogs and cats), laboratory test animal (e.g. mice, rabbits, rats, guinea pigs), performance animal (e.g. racehorses, camels, greyhounds) or captive wild animal. In one example, the subject or patient is a mammal. In one example, the subject or patient is a primate. In one example, the subject or patient is a human. In one example, the subject or patient has not been previously infected with SARS-CoV-2. In another example, the subject or patient has been previously infected with SARS-CoV-2. The terms “reduced expression”, “reduction in expression” or similar, refer to the absence or an observable decrease in the level of protein and/or mRNA product from the target gene e.g., the SARS-CoV-2 nucleocapsid gene or other SARS-CoV-2 gene. The decrease does not have to be absolute, but may be a partial decrease sufficient for there to a detectable or observable change as a result of the RNAi effected by the RNA of the disclosure. The decrease can be measured by determining a decrease in the level of mRNA and/or protein product from a target nucleic acid relative to a cell lacking the RNA, or expression construct, and may be as little as 1%, 5% or 10%, or may be absolute i.e., 100% inhibition. The effects of the decrease may be determined by examination of the outward properties i.e., quantitative and/or qualitative phenotype of the cell or organism, and may also include an assessment of the viral load following administration of a RNAi of the disclosure. As used herein, “long COVID” refers to when symptoms of a SARS-CoV-2 infection remain, or develop, long after the initial SARS-CoV-2 infection. These symptoms include, but are not limited to, extreme fatigue, shortness of breath, heart palpitations, chest pain or tightness, problems with memory and/or concentration “brain fog”, changes to taste and/or smell and joint or muscle pain. Agents for RNAi In one example, the present disclosure provides a RNA, i.e., capable of eliciting RNAi, wherein the RNA comprises an antisense sequence of at least 19 nucleotides in length and a sense sequence, wherein the antisense sequence is substantially complementary to a RNA transcript encoded by a region of the SARS-CoV-2 genome set forth in Table 1. For example, the RNA of the disclosure will comprise an antisense sequence which is less than 30 nucleotides in length. For example, suitable antisense sequences may be in the range of 19-29 nucleotides in length. In one example, the antisense sequence may be 19 nucletoides in length. In one example, the antisense sequence is substantially complementary to a RNA transcript encoded by Region 1 set forth in Table 1. For example, the antisense sequence may be substantially complementary to a RNA transcript encoded by Region 1 set forth in Table 1 and contain 1 mismatch base relative thereto. For example, the antisense sequence may be 95% complementary to a RNA transcript encoded by Region 1 set forth in Table 1. In another example, the antisense sequence may be 100% complementary to a RNA transcript encoded by Region 1 set forth in Table 1. In one example, the antisense sequence is substantially complementary to a RNA transcript encoded by Region 2 set forth in Table 1. For example, the antisense sequence may be substantially complementary to a RNA transcript encoded by Region 2 set forth in Table 1 and contain 1 mismatch base relative thereto. For example, the antisense sequence may be 95% complementary to a RNA transcript encoded by Region 2 set forth in Table 1. In another example, the antisense sequence may be 100% complementary to a RNA transcript encoded by Region 2 set forth in Table 1. In one example, the antisense sequence is substantially complementary to a RNA transcript encoded by Region 3 set forth in Table 1. For example, the antisense sequence may be substantially complementary to a RNA transcript encoded by Region 3 set forth in Table 1 and contain 1 mismatch base relative thereto. For example, the antisense sequence may be 95% complementary to a RNA transcript encoded by Region 3 set forth in Table 1. In another example, the antisense sequence may be 100% complementary to a RNA transcript encoded by Region 3 set forth in Table 1. In one example, the antisense sequence is substantially complementary to a RNA transcript encoded by Region 4 set forth in Table 1. For example, the antisense sequence may be substantially complementary to a RNA transcript encoded by Region 4 set forth in Table 1 and contain 1 mismatch base relative thereto. For example, the antisense sequence may be 95% complementary to a RNA transcript encoded by Region 4 set forth in Table 1. In another example, the antisense sequence may be 100% complementary to a RNA transcript encoded by Region 4 set forth in Table 1. In one example, the antisense sequence is substantially complementary to a RNA transcript encoded by Region 5 set forth in Table 1. For example, the antisense sequence may be substantially complementary to a RNA transcript encoded by Region 5 set forth in Table 1 and contain 1 mismatch base relative thereto. For example, the antisense sequence may be 95% complementary to a RNA transcript encoded by Region 5 set forth in Table 1. In another example, the antisense sequence may be 100% complementary to a RNA transcript encoded by Region 5 set forth in Table 1. In one example, the antisense sequence is substantially complementary to a RNA transcript encoded by Region 6 set forth in Table 1. For example, the antisense sequence may be substantially complementary to a RNA transcript encoded by Region 6 set forth in Table 1 and contain 1 mismatch base relative thereto. For example, the antisense sequence may be 95% complementary to a RNA transcript encoded by Region 6 set forth in Table 1. In another example, the antisense sequence may be 100% complementary to a RNA transcript encoded by Region 6 set forth in Table 1. In one example, the antisense sequence is substantially complementary to a RNA transcript encoded by Region 7 set forth in Table 1. For example, the antisense sequence may be substantially complementary to a RNA transcript encoded by Region 7 set forth in Table 1 and contain 1 mismatch base relative thereto. For example, the antisense sequence may be 95% complementary to a RNA transcript encoded by Region 7 set forth in Table 1. In another example, the antisense sequence may be 100% complementary to a RNA transcript encoded by Region 7 set forth in Table 1. In one example, the antisense sequence is substantially complementary to a RNA transcript encoded by Region 8 set forth in Table 1. For example, the antisense sequence may be substantially complementary to a RNA transcript encoded by Region 8 set forth in Table 1 and contain 1 mismatch base relative thereto. For example, the antisense sequence may be 95% complementary to a RNA transcript encoded by Region 8 set forth in Table 1. In another example, the antisense sequence may be 100% complementary to a RNA transcript encoded by Region 8 set forth in Table 1. In one example, the RNA of the disclosure comprises is a RNA comprising an antisense sequence which is substantially complementary to a RNA transcript encoded by Region 4, Region 6 or Region 7 set forth in Table 1 as described herein. In one example, the RNA of the disclosure is a short interfering RNA (siRNA) duplex. In another example, the RNA of the disclosure is a double-stranded RNA (dsRNA). Exemplary RNAs in accordance with the present disclosure comprise corresponding effector and sense sequences as described in Table 2. In one example, the corresponding effector and sense sequences of the RNAs may be provided as separate nucleic acids which are duplexed (dsRNA) e.g., by Watson-Crick base pairing. In one example, the disclosure provides a RNA, i.e., capable of eliciting RNAi, wherein the RNA comprises an antisense sequence and a sense sequence, wherein the antisense sequence consists of a sequence set forth in the column labelled “Antisense” in Table 2. In one example, the sense sequence consists of a sequence set forth in the column labelled “Sense sequence” in Table 2. An exemplary RNA of the disclosure comprises an antisense sequence consisting of the sequence set forth in SEQ ID NO: 9 and a sense sequence consisting of the sequence set forth in SEQ ID NO: 10. An exemplary RNA of the disclosure comprises an antisense sequence consisting of the sequence set forth in SEQ ID NO: 11 and a sense sequence consisting of the sequence set forth in SEQ ID NO: 12. An exemplary RNA of the disclosure comprises an antisense sequence consisting of the sequence set forth in SEQ ID NO: 13 and a sense sequence consisting of the sequence set forth in SEQ ID NO: 14. An exemplary RNA of the disclosure comprises an antisense sequence consisting of the sequence set forth in SEQ ID NO: 15 and a sense sequence consisting of the sequence set forth in SEQ ID NO: 16. An exemplary RNA of the disclosure comprises an antisense sequence consisting of the sequence set forth in SEQ ID NO: 17 and a sense sequence consisting of the sequence set forth in SEQ ID NO: 18. An exemplary RNA of the disclosure comprises an antisense sequence consisting of the sequence set forth in SEQ ID NO: 19 and a sense sequence consisting of the sequence set forth in SEQ ID NO: 20. An exemplary RNA of the disclosure comprises an antisense sequence consisting of the sequence set forth in SEQ ID NO: 21 and a sense sequence consisting of the sequence set forth in SEQ ID NO: 22. An exemplary RNA of the disclosure comprises an antisense sequence consisting of the sequence set forth in SEQ ID NO: 23 and a sense sequence consisting of the sequence set forth in SEQ ID NO: 24. In one example, the disclosure provides a plurality of RNAs, i.e., capable of eliciting RNAi, wherein each RNA comprises an antisense sequence of at least 19 nucleotides in length and a sense sequence, wherein the antisense sequence of each RNA is substantially complementary to a RNA transcript encoded by a region of the SARS-CoV-2 genome set forth in Table 1. For example, each RNA of the plurality comprises an antisense sequence which is less than 30 nucleotides in length. For example, suitable antisense sequences may be in the range of 19-29 nucleotides in length. In one example, the antisense sequences may be 22 nucleotides in length. A plurality of RNAs in accordance with the present disclosure may be any one or more of the eight RNAs as described herein. In one example, the plurality of RNAs comprises at least one RNAs described herein. In another example, the plurality of RNAs comprises at least two RNAs described herein. In another example, the plurality of RNAs comprises at least three RNAs described herein. In one example, the plurality of RNAs comprises at least four RNAs described herein. In one example, the plurality of RNAs comprises at least five RNAs described herein. In one example, the plurality of RNAs comprises at least six RNAs described herein. In one example, the plurality of RNAs comprises at least seven RNAs described herein. In one example, the plurality of RNAs comprises eight RNAs described herein. Thus, the plurality of RNAs in accordance with the present disclosure may comprise any one or more of the RNAs described herein comprising an antisense sequence substantially complementary to a RNA transcript encoded by a region of the SARS-CoV-2 genome set forth in Table 1. In one example, the plurality of RNAs described herein are provided together as a single composition. In another example, the plurality of RNAs described herein are provided as multiple compositions. For example, each of the RNAs of the plurality may be provided separately. Alternatively, at least one RNA of the plurality may be provided separately and two or more of the plurality provided together in a composition. In one example, the antisense sequence of a RNA in the plurality is substantially complementary to a RNA transcript encoded by Region 4 in Table 1. In one example, the antisense sequence of a RNA in the plurality is substantially complementary to a RNA transcript encoded by Region 6 in Table 1. In one example, the antisense sequence of a RNA in the plurality is substantially complementary to a RNA transcript encoded by Region 7 in Table 1. In one example, the disclosure provides a plurality of RNA i.e., capable of eliciting RNAi, wherein at least one RNA comprises an antisense sequence of at least 19 nucleotides in length and a sense sequence, wherein the antisense sequence of each RNA is substantially complementary to a RNA transcript encoded by a region of the SARS-CoV-2 genome set forth in Table 1. Thus, in one example, the plurality of RNAs comprises at least one RNA selected from the group consisting of: a RNA comprising an antisense sequence set forth in SEQ ID NO:9 and a sense sequence set forth in SEQ ID NO:10; a RNA comprising an antisense sequence set forth in SEQ ID NO:11 and a sense sequence set forth in SEQ ID NO:12; a RNA comprising an antisense sequence set forth in SEQ ID NO:13 and a sense sequence set forth in SEQ ID NO:14; a RNA comprising an antisense sequence set forth in SEQ ID NO:15 and a sense sequence set forth in SEQ ID NO:16; a RNA comprising an antisense sequence set forth in SEQ ID NO:17 and a sense sequence set forth in SEQ ID NO: 18; a RNA comprising an antisense sequence set forth in SEQ ID NO:19 and a sense sequence set forth in SEQ ID NO:20; or a RNA comprising an antisense sequence set forth in SEQ ID NO:21 and a sense sequence set forth in SEQ ID NO:22; and a RNA comprising an antisense sequence set forth in SEQ ID NO:23 and a sense sequence set forth in SEQ ID NO:24. RNA of the disclosure may comprise either synthetic RNAs. Synthetic RNAs may be manufactured by methods known in the art such as by typical oligonucleotide synthesis, and may incorporate chemical modifications to increase half-life and/or efficacy of the siRNA agent, and/or to allow for a more robust delivery formulation. Many chemical modifications of oligonucleotides are known and well described in the art. In one example, substantially all of the nucleotides of a RNA of the disclosure are modified. In other example, all of the nucleotides of a RNA of the disclosure are modified. RNAs of the disclosure in which "substantially all of the nucleotides are modified" are largely but not wholly modified and can include not more than 5, 4, 3, 2, or 1 unmodified nucleotides. In one example, the RNA of the disclosure comprises one or more overhang regions and/or capping groups at the 3'-end, 5'-end, or both ends of one or both strands of the duplex. The overhang regions can be 1-6 nucleotides in length, for instance 2-6 nucleotides in length, 1-5 nucleotides in length, 2-5 nucleotides in length, 1-4 nucleotides in length, 2-4 nucleotides in length, 1-3 nucleotides in length, 2-3 nucleotides in length, or 1-2 nucleotides in length. The overhangs can be the result of one strand being longer than the other, or the result of two strands of the same length being staggered. The overhang can form a mismatch with the target mRNA or it can be complementary to the gene sequences being targeted or can be another sequence. The first and second strands can also be joined, e.g., by additional bases to form a hairpin, or by other non-base linkers. In one example, the nucleotides in the overhang region of the RNA each independently are a modified or unmodified nucleotide including, but no limited to 2'-sugar modified, such as, 2-F, 2'-O-methyl, thymidine (T), deoxy-thymidine (dT), 2'-O-methoxyethyl-5-methyluridine (Teo), 2'-O-methoxyethyladenosine (Aeo), 2'-O-methoxyethyl-5-methylcytidine (m5Ceo), and any combinations thereof. For example, dTdT can be an overhang sequence for either end on either strand. The overhang can form a mismatch with the target mRNA or it can be complementary to the gene sequences being targeted or can be another sequence. The 5'- or 3'-overhangs at the sense strand, antisense strand or both strands of the RNA can be phosphorylated. In some examples, the overhang region(s) contains two nucleotides having a phosphorothioate between the two nucleotides, where the two nucleotides can be the same or different. In one example, the RNA contains only a single overhang, which can strengthen the interference activity of the RNA, without affecting its overall stability. For example, the single- stranded overhang is be located at the 3'-terminal end of the antisense sequence or, alternatively, at the 3'-terminal end of the sense sequence. In one example, the RNA also comprises a blunt end, located at the 5'-end of the sense sequence (or the 3'-end of the antisense sequence ) or vice versa. Any RNA disclosed herein can include one or more modifications, including any modification described herein. Modifications include, for example, end modifications, e.g., 5'- end modifications (phosphorylation, conjugation, inverted linkages) or 3'-end modifications (conjugation, DNA nucleotides, inverted linkages, etc.); base modifications, e.g., replacement with stabilizing bases, destabilizing bases, or bases that base pair with an expanded repertoire of partners, removal of bases (abasic nucleotides), or conjugated bases; sugar modifications (e.g., at the 2'-position or 4'-position) or replacement of the sugar; and/or backbone modifications, including modification or replacement of the phosphodiester linkages. Specific examples of RNAs useful in the disclosure include, but are not limited to RNAs containing modified backbones or no natural internucleoside linkages. RNAs having modified backbones include, among others, those that do not have a phosphorus atom in the backbone. For the purposes of this specification, and as sometimes referenced in the art, modified RNAs that do not have a phosphorus atom in their internucleoside backbone can also be considered to be oligonucleosides. In some example, a modified RNA will have a phosphorus atom in its internucleoside backbone. Representative U.S. patents that teach the preparation of phosphorus- containing linkages include, but are not limited to, U.S. Pat. Nos.7,015,315; 7,041,816; 7,273,933; 7,321,029; and US Pat RE39464. Modified RNA backbones that do not include a phosphorus atom therein have backbones that are formed by short chain alkyl or cycloalkyl internucleoside linkages, mixed heteroatoms and alkyl or cycloalkyl internucleoside linkages, or one or more short chain heteroatomic or heterocyclic internucleoside linkages. These include those having morpholino linkages (formed in part from the sugar portion of a nucleoside); siloxane backbones; sulfide, sulfoxide and sulfone backbones; formacetyl and thioformacetyl backbones; methylene formacetyl and thioformacetyl backbones; alkene containing backbones; sulfamate backbones; methyleneimino and methylenehydrazino backbones; sulfonate and sulfonamide backbones; amide backbones; and others having mixed N, O, S and CH2 component parts. Representative U.S. patents that teach exemplary forms of these oligonucleosides include, but are not limited to, U.S. Pat. Nos. 5,663,312; 5,633,360; 5,677,437; and 5,677,439. In one example, the RNA of the disclosure comprises only unmodified or natural bases, e.g., as described below. In other examples, the RNAs of the disclosure comprise or are a RNA mimetic, e.g., the backbone, of the nucleotide units are replaced with novel groups. The base units are maintained for hybridization with an appropriate nucleic acid target compound. One such oligomeric compound, a RNA mimetic that has been shown to have excellent hybridization properties, is referred to as a peptide nucleic acid (PNA). In PNA compounds, the sugar backbone of a RNA is replaced with an amide containing backbone, in particular an aminoethylglycine backbone. The nucleobases are retained and are bound directly or indirectly to aza nitrogen atoms of the amide portion of the backbone. Representative U.S. patents that teach the preparation of PNA compounds include, but are not limited to, U.S. Pat. Nos.5,539,082; 5,714,331; and 5,719,262. Modified RNAs can also contain one or more substituted sugar moieties. The RNAs, e.g., dsRNAs, featured herein can include one of the following at the 2'-position: OH; F; O-, S-, or N- alkyl; O-, S-, or N-alkenyl; O-, S- or N-alkynyl; or O-alkyl-O-alkyl, wherein the alkyl, alkenyl and alkynyl can be substituted or unsubstituted C1 to C10 alkyl or C2 to C10 alkenyl and alkynyl. Exemplary suitable modifications include O[(CH₂)_nO]_mCH₃, O(CH₂)_nOCH₃, O(CH₁)_nNH₂, O(CH2)nCH3, O(CH2)nONH2, and O(CH2)nON[(CH2)nCH3)]2, where n and m are from 1 to about 10. Suitably, the modified RNAs may comprise one or more 2’-O-methyl modifications, wherein a methyl group is added to the 2’ hydroxyl of the ribose moiety. Thus, any one or more of the RNAs of SEQ ID NOs: 9-24 and 39-54 may comprise one or more 2’-O-methyl modifications. Any number of riboses in such RNAs may be modified. Suitably, 1, 2, 3, 4, 5, 6 or more riboses may comprise a 2’-O-methyl modification. For example, any one or more of the RNAs of SEQ ID NOs: 9-24 and 39-54 may comprise 1, 2, or 3, and preferably 3, 2’-O-methyl modifications in either or both of the sense and antisense strands. For example, SEQ ID NO: 30 may comprise one or more 2’-O-methyl modifications, such as 32’-O-methyl modifications. These 2’-O-methyl modifications may, for example, be present in consecutive sugar moieties within the RNA. Thus, any one or more of the RNAs of SEQ ID NOs: 9-24 and 39-54 (for example, SEQ ID NO: 30) may comprise 2, 3, or more, (and preferably 3) 2’-O-methyl modifications iin consecutive sugar moieties within the RNA, in either or both of the sense and antisense strands. In one particular example, SEQ ID NO: 30 may comprise 2’-O-methyl modifications at positions 4, 5 and 6 thereof. A RNA can also include nucleobase (often referred to in the art simply as "base") modifications or substitutions. As used herein, "unmodified" or "natural" nucleobases include the purine bases adenine (A) and guanine (G), and the pyrimidine bases thymine (T), cytosine (C) and uracil (U). Modified nucleobases include other synthetic and natural nucleobases such as deoxy-thymine (dT), 5-methylcytosine (5-me-C), 5-hydroxymethyl cytosine, xanthine, hypoxanthine, 2-aminoadenine, 6-methyl and other alkyl derivatives of adenine and guanine, 2- propyl and other alkyl derivatives of adenine and guanine, 2-thiouracil, 2-thiothymine and 2- thiocytosine, 5-halouracil and cytosine, 5-propynyl uracil and cytosine, 6-azo uracil, cytosine and thymine, 5-uracil (pseudouracil), 4-thiouracil, 8-halo, 8-amino, 8-thiol, 8-thioalkyl, 8- hydroxyl anal other 8-substituted adenines and guanines, 5-halo, particularly 5-bromo, 5- trifluoromethyl and other 5-substituted uracils and cytosines, 7-methylguanine and 7- methyladenine, 8-azaguanine and 8-azaadenine, 7-deazaguanine and 7-daazaadenine and 3- deazaguanine and 3-deazaadenine. * The RNA can also be modified to include one or more locked nucleic acids (LNA). A locked nucleic acid is a nucleotide having a modified ribose moiety in which the ribose moiety comprises an extra bridge connecting the 2' and 4' carbons. This structure effectively "locks" the ribose in the 3'-endo structural conformation. The addition of locked nucleic acids to siRNAs has been shown to increase siRNA stability in serum, and to reduce off-target effects (Elmen, J. et al., (2005) Nucleic Acids Research 33(1):439-447). Potentially stabilizing modifications to the ends of RNA can include N- (acetylaminocaproyl)-4-hydroxyprolinol (Hyp-C6-NHAc), N-(caproyl-4-hydroxyprolinol (Hyp- C6), N-(acetyl-4-hydroxyprolinol (Hyp-NHAc), thymidine-2'-O-deoxythymidine (ether), N- (aminocaproyl)-4-hydroxyprolinol (Hyp-C6-amino), 2-docosanoyl-uridine-3''-phosphate, inverted base dT(idT) and others. Disclosure of this modification can be found in PCT Publication No. WO 2011/005861. In one example, a RNA of the disclosure is chemically synthesized. Oligonucleotides (e.g., certain modified oligonucleotides or portions of oligonucleotides lacking ribonucleotides) are synthesized using protocols known in the art, for example as described in Caruthers et al., 1992, Methods in Enzymology 211, 3-19, WO 99/54459, Wincott et al., 1995, Nucleic Acids Res.23, 2677-2684, Wincott et al., 1997, Methods Mol. Bio., 74, 59, Brennan et al., 1998, Biotechnol Bioeng., 61, 33-45, and Brennan, U.S. Pat. No.6,001,311. The synthesis of oligonucleotides makes use of common nucleic acid protecting and coupling groups, such as dimethoxytrityl at the 5'-end, and phosphoramidites at the 3'-end. RNA without modifications are synthesized using procedures as described in Usman et al., 1987, J. Am. Chem. Soc., 109, 7845; Scaringe et al., 1990, Nucleic Acids Res., 18, 5433. These syntheses makes use of common nucleic acid protecting and coupling groups, such as dimethoxytrityl at the 5'-end, and phosphoramidites at the 3'-end that can be used for certain RNA of the disclosure. In certain examples, the RNAs of the disclosure are synthesized, deprotected, and analyzed according to methods described in U.S. Pat. Nos.6,995,259, 6,686,463, 6,673,918, 6,649,751, and/or 6,989,442. In an alternative example, a RNA of the disclosure is synthesized as discrete components and joined together post-synthetically, for example, by ligation (Moore et al., 1992, Science 256, 9923 or WO 93/23569), or by hybridization following synthesis and/or deprotection. Nucleic acids A RNA of the disclosure can be transcribed from a nucleic acid. Accordingly, in one example, the disclosure provides a nucleic acid encoding a RNA of the disclosure. In one example, the nucleic acid is DNA. In another example, the disclosure provides a nucleic acid encoding a plurality of RNAs of the disclosure. In another example, the disclosure provides a plurality of nucleic acids encoding a plurality of RNAs of the disclosure. For example, each nucleic acid of the plurality may encode a single RNA described herein. In another example, one or more nucleic acids encodes a plurality of RNAs e.g., a nucleic acid of the plurality encodes two or more RNAs of the disclosure and another nucleic acid of the plurality encodes one or more RNAs of the disclosure. In one example, the plurality of nucleic acids described herein are provided together e.g., in a single composition. In another example, the plurality of nucleic acids described herein are provided as multiple components e.g., multiple compositions. For example, each of the nucleic acids of the plurality may be provided separately. Alternatively, in an example where at least three nucleic acids of the disclosure are provided, at least one of the nucleic acids may be provided separately and two or more of the plurality provided together. In some examples, a nucleic acid of the disclosure comprises one or more additional elements e.g., to facilitate transcription of the RNA. Expression constructs In one example, a nucleic acid of the disclosure is included within an expression construct. In one example, the expression construct is an expression vector. In another example, the expression vector is a plasmid, e.g., as is known in the art. Carriers In some examples, a RNA or expression construct of the disclosure is in a composition with a carrier. Suitable carriers are known in the art. For example, suitable carriers include but are not limited to a lipid-based carrier, cationic lipid, or liposome nucleic acid complex, a liposome, a micelle, a virosome, a lipid nanoparticle or a mixture thereof. Thus, in one example, the carrier is a lipid nanoparticle. Compositions and methods of treatment A RNA or nucleic acid or expression construct of the disclosure is used in compositions for preventing or treating SARS-CoV-2 infection. The therapeutic compositions of the disclosure may be used alone or in combination with one or more materials, including other antiviral agents. Currently, Paxlovid, Remdesivir, Molnupiravir and Sotrovimab have been approved for treatment of SARS-CoV-2. Since the RNA of the disclosure act against SARS-CoV-2 through a different mechanism to other approved drugs, combination therapy of the agents of the disclosure and other antivirals is expected to significantly increase the efficacy of therapy while substantially reducing the development of drug resistance, e.g., the development of antiviral resistance or rebound, a problem of major concern with antiviral therapy. Compositions will desirably include materials that increase the biological stability of the RNA or expression construct of the disclosure and/or materials that increase the ability of the compositions to penetrate cells selectively. The therapeutic compositions of the disclosure may be administered in pharmaceutically acceptable carriers (e.g., physiological saline), which are selected on the basis of the mode and route of administration, and standard pharmaceutical practice. One having ordinary skill in the art can readily formulate a pharmaceutical composition that comprises a RNA or expression construct of the disclosure. In one example, the composition is formulated as a nasal spray or a mouth spray. Routes of administration include, but are not limited to, intramuscular, intraperitoneal, intradermal, subcutaneous, intravenous, intrathecal, intraarterially, intraoccularly, intranasal and oral as well as transdermal or by inhalation or suppository. Exemplary routes of administration include intravenous, intramuscular, oral, intraperitoneal, intradermal, intraarterial, intranasal and subcutaneous injection. In one example, the composition is formulated for administration orally or intranasally. In one example, the composition is formulated for administration through inhalation. As used herein, “inhalation” is defined as the taking in of the composition described herein into the lungs. Kits The present disclosure also provides a RNA, nucleic acid or expression construct of the disclosure in a kit. The kit may comprise a container. The kit typically contains a RNA or nucleic acid or expression construct of the disclosure with instructions for its administration. In some examples, the kit contains more than one RNA or nucleic acid or expression construct of the disclosure and/or another RNA or nucleic acid or expression construct of the disclosure.

_e^m_o A A_C Uⁿ_{C C} A A_e^C A A U G U^g2₎^’_C A A U A A 3 A G G^{U U} G^{C G} U_{C C C C} - A^C G U U^V_{o >}^{- A}_C U^{G G}C_C A U_C A_C G A^G C G G -_’S⁵ G ( A G^U C A^U G^A C _C A R^e_c A U n U G U^G C _C^U A_C^A U^A_{S e} G U U_e^u G G^{U A} C U A A_C G A^Ah_qt^{e A} G_C U U A^C_C A G A_C Uⁿ_{s C} G_{i n}^{C C} U^A C _C U U A U^h_t^o_{i i}^g_C U_C G A A U G U A G A^A C^w_e R^U C^G C U^U G_C^C C G^G G^s G G G_C G_n^o_i^g_e^r_t^e_g^Dr_Ia^1T_n^o_{- i}^{n 2 g}_o^{n 3 n 4 n 5 n 6 n 7 n 8 n} eⁱ_{o g}ⁱ_oⁱ_oⁱ_oⁱ_oⁱ_oⁱ_o e_g^e_g^e_g^e_g^e_{g g}ⁱ_g1 R_{R R R R}^{e e e}_e^l_{R R R Rb}^a_T U G U_C )_’ G U U_C A A U A^A C U^– G U G_’ U G 3 G G^U C^A A^{A 5} (^G U –_’^A G_C U U C G A^{A C}_C A_{C C}^e_C G A U_c n A^G C G A :⁹_{1 3 5 7 9 :}^{1 1 1}_{1 3 :}¹_:^{1 2}_:²_{5 7} O_{: : : :} O O O O O O O O_:²_:⁵_: N ^{N N N N N N N N} O O O D ^N I^D I^D I^D I^{D N N} I^D I^D I^D I^D I^{D D D} Q_I Q Q Q Q_{I I} E ^E Q Q Q Q Q Q Q S _S^E_S^E_S^E_S^E_S^E_S^E_S^E_S^E_S^E_S^E_S T_d^T_T T_d^d_T^d_T^d_T^T_d^T_{d d}^T_T^d_T^d_T^{d d}_T^T_d^T_d^{T T} G_{d C C C}^d G_{d d} A^G_C^{C T}_d^T_d A_C A G G G A^U A G^C C_{C C}^U G G^G G_C U U A_C U^U_C G A G A U )_{’ C} G G^G U_C U U G^A C U A A_s^{3 –} G^A A_C )^{C C} G A G U C A G G A G U^e_{x ’} C^C ’ _C A U A U G U C^e_l⁵₍^C_C 3 A^{A –}_C A^G U U G U A^{p e}_{c C} U U^{G ’} U A G 5 U_C G G ( C A U^A U_u G U^{d n}_e^G_C A U^A C _C U G_s^u_C A e^s U G A G G^U C^G C^C C A_q^e n _s^A C e U^{G A} C C^C A A N_{e C}^A s_i U_{C C} G G^{s A}_C t G U U A A_C G^{G R}_{n C} G n G U U A A^U G_{C C} U A^l A U U G A G G U U_a^{e n}_si G G o^{t i}_{t n} G^{A A}_{C i} A_C U d_d D_I A^lr_{2 t}^lr 2 ₇⁶₁^{8 1 5 7 0 – D}_I^C_{t -}^C A_{1 2 2 2 3}³ A - A A A A A A A A A R ^{N N N N e i}_l A N N s _Rⁱ_{s R}^{N N N N i}_{s R}ⁱ_{s R}ⁱ_{s R}ⁱ_{s R}ⁱ_{s R}ⁱ_{s R}ⁱ_s^{b N N} a^Ri_Rⁱ_R^{i T}_{s s s} U G U_C )_’ G U U_C A A U A^A C U^– G G_’ U 3 G G^U C^A A^{A 5} (^{G –}_’^A G_C U U_C A C G A^{A C}_{C C}^e_C G A U_c n A G_n^e_S^A C _{: 9}³₁⁴₃⁴₅⁴₇⁴₉⁴₁⁵₃⁵₅ O_{: : : : : : : :} O O O O_:⁵_: N O O O O N ^{N N N N N N N} O D ^N O I^{D N} I^D I^D I^D I^D I^D I^D I^D I^D_I^D Q E Q Q Q Q Q Q Q Q_I Q Q S^E_S^E_S^E_S^E_S^E_S^E_S^E_S^E_S^E_S^E_{S g}ⁿ_a^h_rg G_{C C C} G^e A^G A G G_C^C_vⁿ_a A_C C G^C_C^o G^h_r G A^U C A U U_C^U C G U^he G G_t^U_v G^G A G A A A U A_i w )_{’ C}^o U_C U U G U³ G G_C U A_s^– A_t^{C C} A G^u )_C A G A G U G^e_{x ’} C_{o ’}^{h 3}_C A U A U G U A^A C C^e A_t^G U U G U A_l^{5 p}₍ e ^C c _Ci^{– ’} U A G_C G^w₅ U^A G U_uⁿ U e^G_s⁽ C A U U G^A_C G^d s^u_C^e_e U A U_x^s U_C^G G A G G^U_C^C A_q^{e A} U^{G A} C C_C A_C A_{s C}^e_nl^ep_si U_{C C} G G^C C G^G N_u^t G U U A A n G U U A A^U G_C^R_{e C} U A^{l s}_n^A a^e_{C s}^d A U U G A G G U Uⁿ_i G o^t G i_n A^A A_{ti C}N^dR_d–^{l D 6} A^{– D} r_{t7 Ie}^l A_{2 7 1}⁸₁¹₂⁵₂⁷₂⁰_{3 I}^C- A A A A A A A A^{8 e} A A_b^a N R ^{N i}_R^{N i}_R^{N i}_R^{N N N N N i}_Rⁱ_Rⁱ_Rⁱ_Rⁱ_{R l}^b N R ^N R_{T s s s s s s s s}ⁱ_{s a}^{i i T}_{s s} Examples Example 1 –Target regions for design of siRNAs SARS-CoV-1 and SARS-CoV-2 sequences were collected from NCBI and were analyzed for conserved regions of at least 19 bp in length using Geneious Prime® version 2020.0.5 (Biomatters Ltd, New Zealand). A total of 39 siRNAs (each 19 bp) were identified as potential targets to multiple highly conserved regions of the SARS-CoV-2 genome, which were designed with a 3’dTdT overhang and subsequently synthesized (Invitrogen, Waltham, MA). The custom designed siRNA and virus target sites are listed in Table 4, and lead candidate siRNA sequences are listed in Table 5. Table 4: List of siRNA targeting SARS-CoV-2 sequences. siRNA target region  siRNA name  UTR 2 3 4 5 6 7 17 Table 5: Names and sequences of siRNA shown to protect against SARS-CoV-2. s_iRNA name       ^{SEQ ID  Membrane} _{5`‐AAAGCGUUCGUGAUGUAGCdTdT‐3`  Antisense  15}   Envelope  5`‐GCCAUCCUUACUGCGCUUCdTdT‐3`  Sense  18  early isolate of SARS-CoV-2 (VIC01) using HEKAT10 cells, as described in Example 2. This virus isolate represents an ancestral strain from early 2020 against which siRNA could be rapidly screened. Example 2 – Activity of siRNAs Cell culture HEK293T cells were modified to co-express SARS-CoV-2 entry receptors ACE2 and TMPRSS2, termed HEKAT10 as described (Tea et al., 2021). Cultures were maintained in DMEM supplemented with 10% fetal calf serum (FCS), 5 U/mL penicillin, and 50 mg/mL streptomycin (Gibco, Waltham, MA). Vero E6 cells were maintained in MEM (Gibco, Waltham, MA) supplemented with 10% fetal calf serum (FCS), 1 mM sodium pyruvate, 5 U/mL penicillin, and 50 mg/mL streptomycin. Table 6. SARS CoV‐2 variants used in testing  Variant  Pango lineage  Sequence source and ID  Omicron  B.1.1.529  GISAID: hCoV‐19/Australia/NSW‐RPAH‐1933/2021  HEKAT10 or Vero E6 cells (1.5 x 10⁴) were seeded into a 96 well plate approximately 4 h prior to siRNA transfection. All transfections were performed using Lipofectamine RNAiMAX (Invitrogen, Waltham, MA) as per the manufacturer’s protocol.1 h following siRNA transfection, cultures were challenged with live SARS-CoV-2 at an MOI 0.009 and 0.045 for HEKAT10 and Vero E6 cells, respectively. Cultures investigating multiplexing were transfected with half the original quantity of each siRNA (i.e.2.5 nM for each siRNA), such that the final concentration of total siRNA was equal to that of the manufacturer’s protocol (5 nM). At 72 h post infection, plates were imaged to determine cell survival and supernatant was collected for RT-qPCR analysis. Transfection and infection conditions were scaled to a 12 well plate for Western blot cultures, which were seeded with 1.5 x 10⁵ HEKAT10 cells. Drug treatment and SARS-CoV-2 infection Vero E6 cultures were treated with either Remdesivir or Sotrovimab and the antiviral activity was measured using the cell survival assay and virus nucleocapsid mRNA levels by RT- qPCR. Remdesivir was used at concentrations 1 µM and 5 µM. Sotrovimab was used at concentrations 372 ng/mL and 1860 ng/mL. These concentrations represented their approximate IC50 based on previous data (Sanna et al., 2022; Schooley et al., 2021). In both instances the drugs were diluted using the Vero E6 culture media and administered approximately 1 hr prior to SARS-CoV-2 infection. The conditions of cell seeding and infection are the same as those described above. Cell survival assay Cells were stained with NucBlue (Invitrogen, Waltham, MA) 48 h post SARS-CoV-2 infection. At 72 h post infection, wells were imaged in both brightfield (white light) and blue light spectrums using an InCell Analyzer 2500 HS (Cytiva, Marlborough, MA) plate reader and 10X Nikon camera. INCarta Image Analysis Software (Cytiva, Marlborough, MA) was used to determine nuclei counts for the quantification of cell survival. Cell survival was determined relative to untreated cultures. Real-time quantitative PCR detection of SARS-CoV-2 nucleocapsid Culture supernatants were collected 72 h post SARS-CoV-2 infection. For RT-qPCR analysis, RNA extraction was performed using the Monarch® Total RNA Miniprep Kit (NEB, Massachusetts, USA, T2010) as per the manufacturer’s instructions. RNA samples were prepared using the Luna® Universal Probe One-Step RT-qPCR Kit (NEB, E3006) as per the manufacturer’s kit instructions and RT-qPCRs were performed on a CFX96 Touch™ Real-Time PCR detection system (Bio-Rad Laboratories, California, USA) using cycling conditions: 55°C for 10 min, 95°C for 1 min, then 45 cycles of 95°C for 10 s, 60°C for 30 s. Primer and probes used include; Fwd 5’- GAC CCC AAA ATC AGC GAA AT -3’ (SEQ ID NO: 27), Rev 5’ -TCT GGT TAC TGC CAG TTG AAT CTG- 3’(SEQ ID NO: 28) and Probe 5’ -FAM-ACC CCG CAT TAC GTT TGG TGG ACC-BHQ1 -3’ (SEQ ID NO: 29)(IDT, 10006606). Viral load was quantified using a control plasmid containing the complete SARS-CoV-2 nucleocapsid gene (IDT, 10006625). SARS-CoV-2 nucleocapsid immunoblotting HEKAT10 cells were transfected with siRNAs, followed by SARS-CoV-2 challenge as described above.72 hours post infection, whole cell lysate (WCL) were obtained using Glo Lysis Buffer (Promega, E266A), supplemented with mini cOmplete ULTRA protease inhibitor cocktail tablets, EDTA672 free (Roche, 05892791001) and 50 U/mL Pierce Universal Nuclease for Cell Lysis (ThermoFisher Scientific, 88700). SDS-PAGE and membrane transfer was performed using the Mini Gel Tank system (Life Technologies). WCLs were mixed with sample buffer and reducing agent and heated at 95°C for 5 min, prior to being separated on a NuPAGE™ 4-12% Bis-Tris Gel (NP0323) at 200 V for 39 min. Separated proteins were transferred onto a 0.45 µm polyvinylidene difluoride membrane (EMD Millipore, IPVH00010) at 20 V for 1 h, blocked for 1-2 h at room temperature and immunoblotted with rabbit Anti- SARS-CoV-2 Nucleocapsid antibody (1:1000, ThermoFisher Scientific, PA5-114448), or mouse Anti-GAPDH Loading Control (1:1000, Abcam, ab9484). Membranes were washed three times for 5 min with 0.1% Triton X-100/DPBS, followed by addition of secondary antibodies: goat Anti-Rabbit-HRP (1:10000, Bio Rad Laboratories, 1706515) or goat Anti-Mouse-HRP (1:10,000, Bio Rad Laboratories, 1706516) for 1 h. For Nucleocapsid immunoblotting, blocking and antibody diluent was performed using 2.5% (w/v) skimmed milk/DPBS. For GAPDH immunoblotting, blocking was performed using 5% (w/v) BSA/DPBS (Sigma-Aldrich, A1933) and the antibody was diluted in DPBS. Membranes were developed in Clarity Western ECL Substrate (Bio Rad Laboratories, 6901705061), followed by visualization using GeneSys image acquisition software on a G:BOX Chemi XX6 (Syngene). Gel analysis was performed using ImageJ 1.52a (NIH) and densitometry calculated relative to GAPDH. Additional SARS-CoV-2 infected controls were created using conditions above, harvesting cell lysates at 48 hours post infection to confirm accuracy of Nucleocapsid antibody. RT-qPCR detection of interferon stimulated gene expression Vero E6 cells were transfected with siRNA for 72 hours, and RNA extracted using the Monarch® Total RNA Miniprep Kit (NEB, Massachusetts, USA, T2010) as per the manufacturer’s instructions. RNA samples were prepared using the Luna® Universal One-Step RT-qPCR Kit (NEB, E3005) as per the manufacturer’s kit instructions and RT-qPCRs were performed on a CFX96 Touch™ Real-Time PCR detection system (Bio-Rad Laboratories, California, USA) using cycling conditions: 55°C for 10 m, 95°C for 1 m, then 45 cycles of 95°C for 10 s, 60°C for 30 s, and a melt curve of 60-95°C with 0.5°C increments for 5 s. The mRNA expression levels of three type I interferon (IFN) response genes, ISG20, Viperin and IFIT1 were detected, and data was normalized to GAPDH. The following primers were utilized: ISG20; Fwd 5′- TGT GCT GTA CGA CAA GTT CAT CC -3′ (SEQ ID NO: 30) and Rev 5′- TCA TGT CCT CTT TCA GTG CCT G -3′ (SEQ ID NO: 31), Viperin; Fwd 5′- GGA AGC TGG TAT GGA GAA GAT CAA C -3’ (SEQ ID NO: 32) and Rev 5′- GCC AAT AAG GAC ATT GAC TTC CTC -3′ (SEQ ID NO: 33), IFIT1; Fwd 5′- AAC CAA GCA AGT GTG AGG AGT C -3′ (SEQ ID NO: 34) and Rev 5’- CCG CTC ATA ATT CTT TCC TCC ACA -3’ (SEQ ID NO: 35) and GAPDH; Fwd 5’- CAT CAC CAT CTT CCA GGA ACG A -3’ (SEQ ID NO: 36) and Rev 5’- GTT CAC ACC CAT GAC AAA CAT AGG -3’(SEQ ID NO: 37). ISG20, Viperin and IFIT1 have all been used to detect the downstream effects of the type I IFN response induced by RNA duplexes as previously reported (Ahlenstiel et al., 2015). Conservation analyses of siRNA across SARS-CoV-2 variants Publicly available SARS-CoV-2 sequences were downloaded from GISAID. Sequences were analyzed for complete conservation of the 19 bp siRNA target site in Geneious Prime® version 2021.2.2. If the siRNA target site was fully conserved in all of the analyzed sequences in a given variant, a result of 100% conserved was yielded. Statistical analysis Cell survival and RT qPCR data are shown as mean ± SEM, with statistical tests performed using a one-way ANOVA and statistical significance was measured compared to the siRNA-control populations. Western blot data are shown as mean ± SEM and statistical comparisons were made between the siRNA-control and therapeutic siRNA using an unpaired t test. A P value of <0.05 was considered statistically significant. Analyses were performed using GraphPad Prism Version 8.0 (GraphPad Software, San Diego, CA). Results Candidate siRNAs improve cell survival against SARS-CoV-2 in HEKAT10 cells The panel of 39 siRNAs were designed to conserved regions of the SARS-CoV and SARS-CoV-2 genomes. These were screened for antiviral effectiveness against SARS-CoV-2 (Ancestral VIC01 strain) in HEKAT10 cells and the protection from virus-mediated cell death was determined via a novel cell survival assay. The cell survival of siRNA transfected cultures was determined relative to untreated, uninfected cultures, while statistical comparisons were made between infected siRNA-control populations, in order to show significance in improving cell survival. This preliminary screen revealed 19 siRNAs that significantly increased cell survival: siRNAs 1, 2, 3, 7, 9, 13, 14, 16, 17, 18, 20, 21, 25, 27, 30, 33 (all P < 0.0001), 29 (P < 0.001), and 11, 22 (P < 0.01) (Figure 1a). Additionally, protection from cytopathic effect was observed in therapeutic siRNA treated cultures challenged with SARS-CoV-2, which appear morphologically comparable to uninfected HEKAT10 cells, opposed to infected cultures (Figure 1b).16 of the lead candidate siRNAs, which provided the greatest protection and possess antiviral potential against the SARS-CoV-2 variants were explored further. Not only did these siRNA provide significant protection against infection-induced cell death, several of them also provided sufficient protection to allow cell counts to reach that of uninfected control cultures. Antiviral siRNAs protect HEKAT10 cells against SARS-CoV-2 variants The 16 lead candidate siRNAs were screened for antiviral activity against SARS-CoV-2 VOCs; Alpha (Pango lineage B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and VOIs; Zeta (P.2), Kappa (B.1.617.1) using the cell survival assay. Transfection with siRNAs 1, 2, 7, 16, 21, 25, 27, 30 prior to SARS-CoV-2 infection in HEKAT10 cells resulted in a highly significant improvement in relative cell survival in all the tested variants (all P < 0.0001) (Figure 2), with an observed increase in cell survival of up to 93% (Figure 2a). The most significant increase in cell survival was observed in cultures transfected with siRNAs 2, 16, 25, 27, 30 in all variants. In addition to these, other siRNA showed varied levels of protection depending on the SARS-CoV-2 variant, such as siRNA 21 and 25, which showed strong protection in all except Zeta, where a weaker but still significant level of cell survival was observed (Figure 2e). Further, treatment with siRNAs 3, 17 or 18 lead to a significant improvement in all tested variants (all P < 0.0001), except in Zeta, Alpha and Kappa, respectively. This data demonstrates that these novel siRNAs have the potential to provide broad-spectrum antiviral protection. siRNAs reduce viral RNA levels in HEKAT10 cells To further investigate the siRNAs antiviral effectiveness, supernatant was collected 72 h post infection from cultures transfected with the eight most effective siRNAs across all variants and analyzed for the detection of SARS-CoV-2 Nucleocapsid (NC) RNA levels. All siRNAs demonstrated a significant decrease in NC copies/µL against SARS-CoV-2 Beta infection, with a reduction of up to >2 logs, and all siRNA providing significant reductions (P < 0.05) (Figure 3a). Additionally, several siRNA elicited reductions in viral load against the Delta variant, with siRNA 18 reducing viral load by >4 logs (P <0.0001) (Figure 3b), and siRNA 2, 21, 25, 27, and 30 all reducing viral load by between 1 and 3 logs (all P < 0.05) in comparison to infected siRNA-control populations. This data indicates that an increase in cell survival correlates with a marked decrease in viral replication and that the novel cell survival assay is a reliable, rapid screening method for identifying effective antiviral siRNA. siRNAs suppress viral protein levels in HEKAT10 cells To determine whether the siRNA also induced a reduction of virus infection at the protein level, HEKAT10 cells were transfected with the same lead eight candidate siRNAs that demonstrated the most broad-spectrum protection and were challenged with SARS-CoV-2 Beta. Whole cell lysates were collected 72 hours post-infection and immunoblotted for NC protein. Quantification was normalized to GAPDH, and data was made relative to the siRNA-control population. GAPDH was consistently undetectable in infected cultures only, potentially due to high cell death, so additional lysates were obtained 48 hours post-infection whereby GAPDH was detectable to confirm antibody binding (Figure 3c). siRNA 2, 16, 25, and 30 demonstrated the greatest knockdown of relative viral protein (all P < 0.0001), with an observed reduction of up to than 93% when compared to the siRNA-control (Figure 3d). This was followed by siRNAs 18 and 30 (P < 0.001) and 21 and 7 (P < 0.01) which all reduced NC expression by at least 57% (Figure 3d). Overall, a significant improvement in cell survival (Figure 2b) and decrease in nucleocapsid RNA levels (Figure 3a) was accompanied by a reduction of nucleocapsid protein (Figure 3c) further indicating the therapeutic potential of these antiviral siRNA. Antiviral siRNAs protect Vero E6 cells against SARS-CoV-2 Beta, Delta and Omicron variants To determine whether the siRNAs could provide an antiviral response outside of the HEKAT10 cell culture system, the eight lead candidate siRNAs (2, 7, 16, 18, 21, 25, 27, 30) were screened in Vero E6 cells and challenged with SARS-CoV-2 Beta, Delta or Omicron variants. Transfection with siRNAs 2, 7, 16, 18, 27 and 30, prior to Beta infection, resulted in a significant increase in relative cell survival when compared to siRNA-control transfected cultures (all P < 0.0001, Figure 4a). Analysis of the viral NC RNA levels showed all siRNA, except siRNA 16, significantly reduced viral load when compared to the siRNA-control (P < 0.05) (Figure 4b), with siRNA 18, 21, 27, and 30 each reducing viral load by 1-2 logs (P < 0.0001). Similarly, transfection with all siRNAs, except 21, prior to Delta infection also significantly improved relative cell survival (all P < 0.0001, Figure 4c). Additionally, all siRNA, except siRNA 16, significantly reduced viral load of the SARS-CoV-2 Delta variant (P<0.001), with siRNA 18 and 30 reducing viral load by close to 2 logs (P<0.0001) (Figure 4d). Interestingly, siRNA 21 which protected HEKAT10 cells against cell death against Beta and Delta (both P < 0.0001, Figure 2b, d), and siRNA 25 which protected HEKAT10 cells against Beta (P < 0.0001, Figure 2b) did not produce an antiviral response in Vero E6 cells. Transfection with all siRNAs, except 21, prior to Omicron challenge, significantly protected Vero E6 cells from virus-mediated cell death (all P < 0.0001, Figure 4e), with an observed relative cell survival of up to 91%. This corresponded to a significant decrease in viral NC copies, with a reduction of up to 2.5 logs (all P < 0.0001, Figure 4f). Interestingly, while treatment with siRNA 21 resulted in a less pronounced decrease in viral load, a significant decrease was still observed (P < 0.001). This data further highlights that these novel siRNAs continue to display antiviral potency in variants of concern, including those with increasing resistance to clinically marketed antiviral drugs, such as monoclonal antibodies. To explore antiviral siRNAs effectiveness further, Vero E6 cultures were co-transfected with each pair combination of siRNA in a multiplex approach and were challenged with Delta infection. Promisingly, every pair combination significantly improved the relative cell survival outcome when compared to the siRNA-control population (all P < 0.0001), except siRNAs 21 with 25 and 25 with 27, which were not significant (Figure 5a). siRNA pairs 2 and 30, 16 and 30, 18 and 30, 21 and 30 and 25 and 30 demonstrated the greatest protection from cell death, with a mean cell survival of 89, 93, 97, 94 and 91%, respectively. Multiplexed siRNAs yielded similar results to individual siRNA, where all except two combinations (16 with 21 and 16 with 25) induced highly significant reductions in virus NC RNA levels in supernatant (P < 0.0001), with siRNA 18 paired with 30 resulted in a more than 2 log reduction in virus (Figure 5b). This data confirms the identified candidate siRNAs can provide antiviral benefits across cell types, and when used in combination. siRNAs outcompete Remdesivir and Sotrovimab at IC₅₀ concentrations In order to determine if siRNA were comparable in efficacy to clinically used treatment options, three of the top performing siRNAs against SARS-CoV-2 Delta in Vero E6 cells (siRNAs 18, 27, 30) were compared to Remdesivir and Sotrovimab at their reported IC50 and 5X IC50 concentrations (18-20). All treatment conditions showed strong protection against virus- mediated cell death (P < 0.0001) except Remdesivir IC₅₀, which showed no significant antiviral effect (Figure 6a). At 5X IC50, both Remdesivir and Sotrovimab provided the greatest protection against cell death, each significantly greater than the siRNA. However, siRNA 30 was significantly more protective than either Remdesivir or Sotrovimab at IC50 (P < 0.0001). Similarly, treatment with all siRNA resulted in a significant reduction in viral load (P < 0.0001), showing a greater antiviral effect than both Remdesivir (not significant) and Sotrovimab (P<0.05) at their IC₅₀ concentrations, when compared to the untreated control (Figure 6b). While Remdesivir and Sotrovimab at their 5X IC50 concentrations provided a greater protection from cell death and a more pronounced decrease in viral load, simply increasing the concentrations of these drugs is not a viable approach in practice. This data demonstrates that these novel siRNAs, used at low concentrations of 5 nM, display a greater antiviral potency to clinically available SARS-CoV-2 therapies in vitro, and offer an alternative treatment option. Candidate siRNAs do not induce off-target effects To determine whether any of the siRNA have the potential to mediate off-target effects via the interferon pathway, the expression of three interferon-stimulated genes (ISGs) previously reported to detect type I interferon (IFN) responses induced by RNA duplexes were analyzed. The mRNA expression of each ISG was made relative to mock transfected cultures, and statistical comparisons were made between siRNA-control populations and therapeutic siRNA treated cultures. Transfection of Vero E6 cells with siRNA 18, 21, 25 and 27 for 72 hours resulted in no significant expression of ISG20, Viperin or IFIT1 mRNA levels (Figure 7). siRNA 2 and 7 increased ISG20 (P < 0.001 and < 0.0001 respectively, Figure 7a) but had no impact on Viperin (Figure 7b) or IFIT1 (Figure 7c). Surprisingly, transfection with siRNA 30 increased all three ISGs (P < 0.01). As expected, the positive control IFNβ increased the expression of all three genes. This data suggests that there are no obvious off-target effects that might be induced by the siRNA 18, 21, 25 and 27. Antiviral siRNA targets remain highly conserved throughout SARS-CoV-2 lineages Given the sequence specificity of RNAi, designing siRNAs to highly conserved regions of the SARS-CoV-2 genome is crucial for developing broad-spectrum treatment alternatives. To investigate whether our lead siRNA target sequences have been maintained throughout viral evolution, publicly available SARS-CoV-2 genome sequences of VOCs or VOIs were obtained from GISAID and analyzed. The target site of siRNAs 16, 21, 27 and 30 were all highly conserved across all variants, and the complete 19 bp was present in at least 98% of assessed sequences (Figure 8b). Similarly, the 19 bp of siRNAs 18 and 25 were conserved in a minimum of 98% of assessed sequences across all variants, except in the Omicron subvariant BA.5 where 94.9% and 89.2% conservation was observed, respectively. siRNA 2 demonstrated the most variation, however, the full target site was still present in 93-100% of analyzed sequences in all variants except the Omicron subvariant BA.1 (58.6%). However, it should be noted that there is less sequence data available for the SARS-CoV-25’UTR protomer, so the greater variability of siRNA 2 could be partially attributed to the smaller sample sizes. Interestingly, a substitution had occurred in the first nucleotide of siRNA 7 throughout all variants, a mutation which was not present in the VIC01 isolate used for preliminary siRNA screening. However, the remaining 18 bp remained conserved in more than 98% of analyzed sequences, in all variants (data not graphed). With the exception of siRNA 7, the full 19 bp of all siRNAs was highly conserved across all variants and, for the most part, were maintained in 98-100% of analyzed sequences. Additionally, any observed variation in the siRNA virus sequence was as a result of unique mutations, as opposed to persistent nucleotide substitutions, which would indicate an evolutionary advantage. This data further highlights the therapeutic potential of these siRNA due to the high conservation of the 19 bp target site throughout more than 2 years of rapid viral evolution, with particular focus on 18, 21, 25, 27 and 30. Conclusion The inventors have demonstrated that these siRNA provide broad spectrum protective effects against multiple SARS-CoV-2 variants, with lead candidates protecting against all SARS- CoV-2 variants tested. In addition, the inventors have shown that the siRNAs work both individually and in combination to reduce viral RNA levels and improve cell survival of cells infected with SARS-CoV-2. When used individually, some siRNA, including siRNA7, siRNA27, siRNA30, provided near complete protection against cell death (Figure 1a, 2, 4a, c, e) for at least three days. This effect was also clearly evident when visualized using microscopy (Figure 1b), with cell populations observed as much more morphologically similar to uninfected controls than infected controls. The multiplexing of two different antiviral siRNAs clearly demonstrated that potent virus suppression can be achieved by targeting multiple virus regions, with the exception of some combinations, including siRNA 21 or 25 (Figure 5). This provides an advantage of increased breadth in protection over the current vaccine development strategy, which used a single ancestral virus variant that is no longer in circulation and is not as effective due to virus mutation resistance. Additionally, multiplexing siRNAs will be beneficial as SARS-CoV-2 evolves mutations that are resistant to current antiviral treatments, such as Omicron which demonstrates resistance to the majority of monoclonal antibodies (VanBlargan et al., 2022), and further, no longer relies on the host co-receptor TMPRSS2 for virus entry. Based on analyzed sequence data, the majority of all lead antiviral siRNAs maintain their virus target across all SARS-CoV-2 variants, including Omicron, BA.1, BA.2, BA.4 and BA.5 (Figure 8b), suggesting they will be able to maintain virus control as SARS-CoV-2 continues to evolve. Example 3 – Delivery of siRNAs Methods Two Human Embryonic Kidney (HEK)-293T reporter cell lines were generated using separate FG11F-Lentiviral vectors expressing Green Fluorescent Protein (GFP) fused to SARS- CoV-2 proteins Membrane or Nucleocapsid to provide a PC2-approved system for screening the antiviral effect of novel siRNAs encapsulated in fluorescently labelled lipid nanoparticles (LNP). Of the two siRNAs examined, siRNA-18 targets SARS-CoV-2-Membrane (Mem), while siRNA- 25 targets SARS-CoV-2-Nucleocapsid (Nuc). All the cells were cultured in 24-well-plates with Dulbecco's modified Eagle's medium (DMEM) containing 10% fetal bovine serum (FBS) and 1% penicillin-streptomycin. Reporter cell lines without transfection were used as the negative control, and cells transfected with the same specific siRNA by Lipofectamine RNAiMAX (Invitrogen, MA, U.S.A, Cat# 13778150) were applied as the positive control (the dose of siRNA was 10 nM). The experimental group was transfected with 5-fold dose of LNP-siRNA 3.4 uM (50 nM siRNA). In brief, cells were seeded to be 60-80% confluent at transfection in a 24-well plate, then the experimental group and positive control group were subjected to siRNA transfection the following day (Day 0). Cell fixation and flow cytometry were performed daily from the second day (Day 2) to the tenth day after siRNA transfection (Day 10). For data analysis, all GFP expression rates were normalised to those observed in the negative control reporter cell line. At the same time, the ratio of LNP-positive-cell/Single-cell for each sample is also detected and collected. Duplicate wells were carried out for each sample, and the mean was taken for analysis (Figure 9). Results To examine the silencing effect of siRNA18 and siRNA25 delivered via fluorescently labelled LNPs, reporter cell lines expressing SARS-CoV-2 Membrane or Nucleoprotein fused to GFP were treated with 50 nM siRNA18-LNP or 50 nM siRNA25-LNP and directly compared to positive controls, 10 nM siRNA18 or 10 nM siRNA25, transfected via lipofectamine2000 reagent. GFP expression was measured as a surrogate marker of siRNA induced silencing of the targeted SARS-CoV-2 protein fused to GFP. Maximum decreases in GFP expression in Lipofectamine-siRNA-treated cells was reported on day 4 (58.89% for Mem-siRNA18 and 43.73% for Nuc-siRNA25, respectively), while cells treated with 50 mM LNP-siRNA showed the greatest decrease in GFP expression on day 6 (62.13% for Mem-siRNA18 and 55.53% for Nuc-siRNA25, respectively) (Figure 9A and 9C). Following transfection, the number of fluorescently labelled LNP-carrying cells exceeded 90% on both day 2 and day 3, and this trend of higher LNP-positive cell ratio continued until day 6 for the 50 nM LNP-siRNA treatment. Notably, until Day 5, the percentage of LNP positive cells in LNP-siRNA group are still over 98%. However, on Day 7, there was a sharp decrease in the LNP positive cell rate in the 50 nM LNP-siRNA treatment. (Figure 9B and 9D). These data demonstrate that LNP delivered siRNAs, 18 and 25, can successfully silence their SARS-CoV-2 membrane and nucleoprotein targets, respectively, and the LNPs are retained in the cells for up to 6 days post-delivery. Example 4 – Delivery of siRNAs To determine whether antiviral siRNA complexed to LNPs were able to be delivered to Vero E6 cells and silence SARS-CoV-2 infection, a virus challenge was performed and cell survival and nucleocapsid vRNA levels were measured as previously described. Briefly, LNP were complexed to siRNAs 27, 30 (25 nM) or a combination of 27 and 30 (50 nM total) using a NanoAssembler device. Vero E6 cells were treated with LNP-siRNAs and then challenged with Omicron BA.1 strain. Cell survival analysis showed all LNP-siRNA treated cultures (siRNA27, siRNA30, siRNA27 and 30) were observed to have significantly increased cell survival compared to the infected positive control culture (p <0.0001) at both days 3 and 4, although the protection by LNP-siRNAs 27 or 30 individually was less, but still significant at day 4 post infection. In contrast the LNP-siRNA27 and 30 combination treatment maintained cell survival to near the uninfected control cultures (Figure 10). This demonstrates that antiviral siRNAs complexed to LNPs are able to be successfully delivered to Vero E6 cells and can induce cell survival against SARS-CoV-2 Omicron BA.1 virus infection. Nucleocapsid (NC) viral RNA levels were significantly decreased at days 3 and 4 post- infection in all LNP-siRNA treated cultures, particularly in siRNA27 and siRNA30 combinations, compared to the infected positive control with no siRNA treatment (p<0.0001)(Figure 11). This demonstrates that antiviral siRNAs complexed to LNPs are able to be successfully delivered to Vero E6 cells and can potently suppress SARS-CoV-2 Omicron BA.1 virus infection. Example 5 – Delivery of siRNAs in vivo To determine whether antiviral siRNA were able to be effectively delivered and induce virus suppression in vivo using an ACE2 K18 mouse model of SARS-CoV-2 infection, siRNA treatment/s were administered intranasally, followed by virus challenge and measurement of mouse weight, clinical scores and viral mRNA levels in the lung. Mouse groups included Sham + Vehicle (uninfected control), SARS-CoV-2 Scrambled (infected siRNA control), SARS-CoV-2 + Vehicle (Infected control), SARS-CoV-2 siRNA 18 and SARS-CoV-2 siRNA30, with six mice per group. Briefly, a dose of 1mg/kg, i.e. 20 ^g/mouse of naked siRNA in PBS (18, 30 or a Scrambled control) was administered intranasally via a syringe at day -1, then at day 0 mice were challenged with SARS-CoV-2 Delta strain 1x10³ PFU, followed by further 20 ^g siRNA treatments at day 1, 3 and 5 post-infection (Figure 12a). Extensive experiments have shown that this virus dose causes severe disease symptoms requiring euthanasia, such as high viral titres, laboured breathing and extreme lethargy, lung inflammation (inflammatory cells, cytokines/chemokines) and histopathology by day 7 post-infection, with low rates of recovery by day 14 post-infection (Counoupas et al., 2021; Burnett et al., 2021). Body weight measurements post virus challenge showed less reduction in body weight for the mice group treated with siRNA18, although this was still significantly decreased compared to the Sham + Vehicle, untreated control group (P<0.05), while mice treated with other siRNAs (30 or Scrambled control) did not differ from the SARS-CoV-2 + Vehicle infected control (Figure 12b). Clinical scores were improved in both siRNA 18 and siRNA 30 treated mouse groups with all Category 1 scores (yellow) and low Category 2 scores, respectively, compared to the infected and siRNA Scrambled controls (Figure 12c). Viral RNA levels in the lung demonstrated a significantly reduced NC mRNA level in the siRNA18 treated mouse group, compared to the siRNA Scrambled control (P<0.05)(Figure 12d). Category 1 scores (in yellow) indicate a minor disease phenotype; including ruffled fur, decreased activity shallow or increased respiratory rate, and/or 10-20% weight loss. Category 2 scores (in orange) indicate a moderate disease phenotype; including increased respiratory sounds (wheezing, snoring), coughing and sneezing, hunched posture, nasal/eye discharge, loose stool, ungroomed, and/or 20-25% weight loss. Category 3 scores (in red) indicate the most severe disease phenotype; including gasping respiration, head tilt/circling, complete lack of movement, pale or cyanotic ears/nose/feet, 25-30% weight loss and/or moribund. Example 6- siRNA Modifications to decrease interferon pathway responses. Assessment of the lead siRNAs to induce interferon pathway responses was performed by transfecting siRNAs 18, 25, 27 and 30 into HeLa T4+ cells using Lipofectamine RNAiMax and measuring the mRNA levels of four interferon stimulated genes (OAS1, IFIT1, Viperin and ISG20) by RT-qPCR at day 3 post-transfection. Only siRNA30 showed any significant increase in mRNA expression of ISG20 compared to the siRNA Scrambled transfection control (Fig. 13a,b,c,d). In order to decrease the reported interferon stimulated gene responses for siRNA 30, the antisense strand was modified by incorporating O-methylation at positions 4, 5 and 6 (si30- AS456) and the interferon stimulated gene mRNA levels were measured as previously described. The O-methyl modification on the antisense strand at positions 4, 5 and 6, significantly decreased the ISG20 mRNA levels so they were comparable to the siRNA Scrambled transfection control (Fig.13d). Example 7- Combination of at least two siRNAs may provide broad-spectrum coverage A SARS-CoV-2 variant sequence analysis was performed to track the virus evolution and determine the level of siRNA target conservation over the time course of the pandemic, specifically from May 2022 to March 2023. This in silico analysis demonstrated that when a new variant emerged with one nucleotide mismatch to the siRNA sequence (e.g. BA5.2.1 and siRNA 18) another siRNA (e.g. siRNA 30) maintained a 100% match to the target virus sequence (Fig.14a). Additionally, when the BQ variant emerged with one nucleotide mismatch to siRNA 25, the siRNA30 sequence maintained a 100% match to the target virus sequence (Fig.14b). This indicates that at least two siRNA may be used simultaneously to provide broad-spectrum antivirus coverage. It will be appreciated by persons skilled in the art that numerous variations and/or modifications may be made to the above-described embodiments, without departing from the broad general scope of the present disclosure. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive. Any discussion of documents, acts, materials, devices, articles or the like which has been included in the present specification is not to be taken as an admission that any or all of these matters form part of the prior art base or were common general knowledge in the field relevant to the present disclosure as it existed before the priority date of each of the appended claims. References Ahlenstiel C, Mendez C, Lim ST, Marks K, Turville S, Cooper DA, et al. Novel RNA Duplex Locks HIV-1 in a Latent State via Chromatin-mediated Transcriptional Silencing. Mol Ther Nucleic Acids.2015;4:e261. DOI: 10.1038/mtna.2015.31 Burnett DL, Jackson KJL, et al. Immunizations with diverse sarbecovirus receptor-binding domains elicit SARS-CoV-2 neutralizing antibodies against a conserved site of vulnerability. Immunity.2021;54:2908. Counoupas C, Johansen MD, Stella AO, et al. A single dose, BCG-adjuvanted COVID-19 vaccine provides sterilising immunity against SARS-CoV-2 infection. NPJ Vaccines. Nov 30 2021;6(1):143. Sanna V, Satta S, Hsiai T, Sechi M. Development of targeted nanoparticles loaded with antiviral drugs for SARS-CoV-2 inhibition. Eur J Med Chem.2022;231:114121. Schooley RT, Carlin AF, Beadle JR, Valiaeva N, Zhang XQ, Clark AE, et al. Rethinking Remdesivir: Synthesis, Antiviral Activity, and Pharmacokinetics of Oral Lipid Prodrugs. Antimicrob Agents Chemother.2021;65(10):e0115521. Tea F, Ospina Stella A, Aggarwal A, Ross Darley D, Pilli D, Vitale D, et al. SARS-CoV-2 neutralizing antibodies: Longevity, breadth, and evasion by emerging viral variants. PLoS Med. 2021;18(7):e1003656. VanBlargan LA, Errico JM, Halfmann PJ, Zost SJ, Crowe JE, Jr., Purcell LA, et al. An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by therapeutic monoclonal antibodies. Nat Med.2022;28(3):490-5.

Claims

CLAIMS: 1. A plurality of RNAs, comprising at least one RNA comprising an antisense sequence of at least 19 nucleotides in length and a sense sequence, wherein the antisense sequence is substantially complementary to a RNA transcript encoded by a region of the SARS-CoV-2 genome, wherein the region comprises a sequence set forth in any one of SEQ ID NOs: 1-8.

2. The plurality of RNAs of claim 1, comprising at least one RNA selected from the group consisting of: a RNA comprising an antisense sequence set forth in SEQ ID NO:23 and a sense sequence set forth in SEQ ID NO:24; a RNA comprising an antisense sequence set forth in SEQ ID NO:11 and a sense sequence set forth in SEQ ID NO:12; a RNA comprising an antisense sequence set forth in SEQ ID NO:13 and a sense sequence set forth in SEQ ID NO:14; a RNA comprising an antisense sequence set forth in SEQ ID NO:15 and a sense sequence set forth in SEQ ID NO:16; a RNA comprising an antisense sequence set forth in SEQ ID NO:17 and a sense sequence set forth in SEQ ID NO: 18; a RNA comprising an antisense sequence set forth in SEQ ID NO:19 and a sense sequence set forth in SEQ ID NO:20; or a RNA comprising an antisense sequence set forth in SEQ ID NO:21 and a sense sequence set forth in SEQ ID NO:22; and a RNA comprising an antisense sequence set forth in SEQ ID NO:9 and a sense sequence set forth in SEQ ID NO:10.

3. The plurality of RNAs of claim 1 or claim 2, comprising: (a) a RNA comprising an antisense sequence set forth in SEQ ID NO:9 and a sense sequence set forth in SEQ ID NO:10 and a RNA comprising an antisense sequence set forth in SEQ ID NO:11 and a sense sequence set forth in SEQ ID NO:12; (b) a RNA comprising an antisense sequence set forth in SEQ ID NO:9 and a sense sequence set forth in SEQ ID NO:10 and a RNA comprising an antisense sequence set forth in SEQ ID NO:13 and a sense sequence set forth in SEQ ID NO:14; (c) a RNA comprising an antisense sequence set forth in SEQ ID NO:9 and a sense sequence set forth in SEQ ID NO:10 and a RNA comprising an antisense sequence set forth in SEQ ID NO:15 and a sense sequence set forth in SEQ ID NO:16; (d) a RNA comprising an antisense sequence set forth in SEQ ID NO:9 and a sense sequence set forth in SEQ ID NO:10 and a RNA comprising an antisense sequence set forth in SEQ ID NO:19 and a sense sequence set forth in SEQ ID NO:20; (e) a RNA comprising an antisense sequence set forth in SEQ ID NO:9 and a sense sequence set forth in SEQ ID NO:10 and a RNA comprising an antisense sequence set forth in SEQ ID NO:21 and a sense sequence set forth in SEQ ID NO:22; (f) a RNA comprising an antisense sequence set forth in SEQ ID NO:9 and a sense sequence set forth in SEQ ID NO:10 and a RNA comprising an antisense sequence set forth in SEQ ID NO:23 and a sense sequence set forth in SEQ ID NO:24; (g) a RNA comprising an antisense sequence set forth in SEQ ID NO:11 and a sense sequence set forth in SEQ ID NO:12 and a RNA comprising an antisense sequence set forth in SEQ ID NO:13 and a sense sequence set forth in SEQ ID NO:14; (h) a RNA comprising an antisense sequence set forth in SEQ ID NO:11 and a sense sequence set forth in SEQ ID NO:12 and a RNA comprising an antisense sequence set forth in SEQ ID NO:15 and a sense sequence set forth in SEQ ID NO:16; (i) a RNA comprising an antisense sequence set forth in SEQ ID NO:11 and a sense sequence set forth in SEQ ID NO:12 and a RNA comprising an antisense sequence set forth in SEQ ID NO:19 and a sense sequence set forth in SEQ ID NO:20; (j) a RNA comprising an antisense sequence set forth in SEQ ID NO:11 and a sense sequence set forth in SEQ ID NO:12 and a RNA comprising an antisense sequence set forth in SEQ ID NO:21 and a sense sequence set forth in SEQ ID NO:22; (k) a RNA comprising an antisense sequence set forth in SEQ ID NO:11 and a sense sequence set forth in SEQ ID NO:12 and a RNA comprising an antisense sequence set forth in SEQ ID NO:23 and a sense sequence set forth in SEQ ID NO:24; (l) a RNA comprising an antisense sequence set forth in SEQ ID NO:13 and a sense sequence set forth in SEQ ID NO:14 and a RNA comprising an antisense sequence set forth in SEQ ID NO:15 and a sense sequence set forth in SEQ ID NO:16; (m) a RNA compmrising an antisense sequence set forth in SEQ ID NO:13 and a sense sequence set forth in SEQ ID NO:14 and a RNA comprising an antisense sequence set forth in SEQ ID NO:19 and a sense sequence set forth in SEQ ID NO:20; (n) a RNA comprising an antisense sequence set forth in SEQ ID NO:13 and a sense sequence set forth in SEQ ID NO:14 and a RNA comprising an antisense sequence set forth in SEQ ID NO:21 and a sense sequence set forth in SEQ ID NO:22; (o) a RNA comprising an antisense sequence set forth in SEQ ID NO:13 and a sense sequence set forth in SEQ ID NO:14 and a RNA comprising an antisense sequence set forth in SEQ ID NO:23 and a sense sequence set forth in SEQ ID NO:24; (p) a RNA comprising an antisense sequence set forth in SEQ ID NO:15 and a sense sequence set forth in SEQ ID NO:16 and a RNA comprising an antisense sequence set forth in SEQ ID NO:17 and a sense sequence set forth in SEQ ID NO: 18; (q) a RNA comprising an antisense sequence set forth in SEQ ID NO:15 and a sense sequence set forth in SEQ ID NO:16 and a RNA comprising an antisense sequence set forth in SEQ ID NO:19 and a sense sequence set forth in SEQ ID NO:20; (r) a RNA comprising an antisense sequence set forth in SEQ ID NO:15 and a sense sequence set forth in SEQ ID NO:16 and a RNA comprising an antisense sequence set forth in SEQ ID NO:21 and a sense sequence set forth in SEQ ID NO:22; (s) a RNA comprising an antisense sequence set forth in SEQ ID NO:15 and a sense sequence set forth in SEQ ID NO:16 and a RNA comprising an antisense sequence set forth in SEQ ID NO:23 and a sense sequence set forth in SEQ ID NO:24; (t) a RNA comprising an antisense sequence set forth in SEQ ID NO:17 and a sense sequence set forth in SEQ ID NO: 18 and a RNA comprising an antisense sequence set forth in SEQ ID NO:19 and a sense sequence set forth in SEQ ID NO:20; (u) a RNA comprising an antisense sequence set forth in SEQ ID NO:17 and a sense sequence set forth in SEQ ID NO: 18 and a RNA comprising an antisense sequence set forth in SEQ ID NO:21 and a sense sequence set forth in SEQ ID NO:22; (v) a RNA comprising an antisense sequence set forth in SEQ ID NO:17 and a sense sequence set forth in SEQ ID NO: 18 and a RNA comprising an antisense sequence set forth in SEQ ID NO:23 and a sense sequence set forth in SEQ ID NO:24; (w) a RNA comprising an antisense sequence set forth in SEQ ID NO:19 and a sense sequence set forth in SEQ ID NO:20 and a RNA comprising an antisense sequence set forth in SEQ ID NO:21 and a sense sequence set forth in SEQ ID NO:22; (x) a RNA comprising an antisense sequence set forth in SEQ ID NO:19 and a sense sequence set forth in SEQ ID NO:20 and a RNA comprising an antisense sequence set forth in SEQ ID NO:23 and a sense sequence set forth in SEQ ID NO:24; (y) a RNA comprising an antisense sequence set forth in SEQ ID NO:21 and a sense sequence set forth in SEQ ID NO:22 and a RNA comprising an antisense sequence set forth in SEQ ID NO:23 and a sense sequence set forth in SEQ ID NO:24.

4. The plurality of RNAs of claim 3, comprising: (a) a RNA comprising an antisense sequence set forth in SEQ ID NO:9 and a sense sequence set forth in SEQ ID NO:10 and a RNA comprising an antisense sequence set forth in SEQ ID NO:23 and a sense sequence set forth in SEQ ID NO:24; (b) a RNA comprising an antisense sequence set forth in SEQ ID NO:13 and a sense sequence set forth in SEQ ID NO:14 and a RNA comprising an antisense sequence set forth in SEQ ID NO:23 and a sense sequence set forth in SEQ ID NO:24; (c) a RNA comprising an antisense sequence set forth in SEQ ID NO:15 and a sense sequence set forth in SEQ ID NO:16 and a RNA comprising an antisense sequence set forth in SEQ ID NO:23 and a sense sequence set forth in SEQ ID NO:24; (d) a RNA comprising an antisense sequence set forth in SEQ ID NO:17 and a sense sequence set forth in SEQ ID NO: 18 and a RNA comprising an antisense sequence set forth in SEQ ID NO:23 and a sense sequence set forth in SEQ ID NO:24; (e) a RNA comprising an antisense sequence set forth in SEQ ID NO:19 and a sense sequence set forth in SEQ ID NO:20 and a RNA comprising an antisense sequence set forth in SEQ ID NO:23 and a sense sequence set forth in SEQ ID NO:24; (f) a RNA comprising an antisense sequence set forth in SEQ ID NO:15 and a sense sequence set forth in SEQ ID NO:16 and a RNA comprising an antisense sequence set forth in SEQ ID NO:19 and a sense sequence set forth in SEQ ID NO:20; (g) a RNA comprising an antisense sequence set forth in SEQ ID NO:9 and a sense sequence set forth in SEQ ID NO:10 and a RNA comprising an antisense sequence set forth in SEQ ID NO:21 and a sense sequence set forth in SEQ ID NO:22; (h) a RNA comprising an antisense sequence set forth in SEQ ID NO:11 and a sense sequence set forth in SEQ ID NO:12 and a RNA comprising an antisense sequence set forth in SEQ ID NO:21 and a sense sequence set forth in SEQ ID NO:22; (i) a RNA comprising an antisense sequence set forth in SEQ ID NO:13 and a sense sequence set forth in SEQ ID NO:14 and a RNA comprising an antisense sequence set forth in SEQ ID NO:21 and a sense sequence set forth in SEQ ID NO:22; (j) a RNA comprising an antisense sequence set forth in SEQ ID NO:15 and a sense sequence set forth in SEQ ID NO:16 and a RNA comprising an antisense sequence set forth in SEQ ID NO:21 and a sense sequence set forth in SEQ ID NO:22; (k) a RNA comprising an antisense sequence set forth in SEQ ID NO:17 and a sense sequence set forth in SEQ ID NO: 18 and a RNA comprising an antisense sequence set forth in SEQ ID NO:21 and a sense sequence set forth in SEQ ID NO:22; (l) a RNA comprising an antisense sequence set forth in SEQ ID NO:19 and a sense sequence set forth in SEQ ID NO:20 and a RNA comprising an antisense sequence set forth in SEQ ID NO:21 and a sense sequence set forth in SEQ ID NO:22; (m) a RNA comprising an antisense sequence set forth in SEQ ID NO:21 and a sense sequence set forth in SEQ ID NO:22 and a RNA comprising an antisense sequence set forth in SEQ ID NO:23 and a sense sequence set forth in SEQ ID NO:24.

5. The plurality of RNAs of claim 3 or claim 4, comprising a RNA comprising an antisense sequence set forth in SEQ ID NO:15 and a sense sequence set forth in SEQ ID NO:16 and a RNA comprising an antisense sequence set forth in SEQ ID NO:19 and a sense sequence set forth in SEQ ID NO:20.

6. The plurality of RNAs of any one of claims 1 to 5, wherein the RNA is a short interfering RNA (siRNA).

7. A nucleic acid comprising a DNA sequence which encodes at least one RNA as defined in any one of claims 1 to 6.

8. An expression vector comprising the DNA sequence of claim 7.

9. A composition comprising the plurality of RNAs of any one of claims 1 to 6 or the nucleic acid of claim 7 or an expression vector of claim 8.

10. The composition of claim 9, further comprising one or more pharmaceutically acceptable carriers.

11. The composition of claim 10, wherein the carrier is a lipid nanoparticle.

12. The composition of any one of claims 9 to 11, wherein the composition is formulated for administration intranasally or orally.

13. The composition of any one of claims 9 to 11, wherein the composition is formulated for administration through inhalation.

14. A method of treating or preventing a SARS-CoV-2 infection in a subject, comprising administering to the subject a therapeutically effective amount of the plurality of RNAs of any one of claims 1 to 6 or the nucleic acid of claim 7 or the expression vector of claim 8 or the composition of any one of claims 9 to 13.

15. A method of reducing SARS-CoV-2 viral load in a subject infected with SARS-CoV-2, comprising administering to the subject a therapeutically effective amount of the plurality of RNAs of any one of claims 1 to 6 or the nucleic acid of claim 7 or the expression vector of claim 8 or the composition of any one of claims 9 to 13.

16. A method of reducing severity of symptoms associated with SARS-CoV-2 infection in a subject, comprising administering to the subject a therapeutically effective amount of the plurality of RNAs of any one of claims 1 to 6 or the nucleic acid of claim 7 or the expression vector of claim 8 or the composition of any one of claims 9 to 13.

17. A method of reducing the infectivity of SARS-CoV-2 in a subject infected with SARS- CoV-2, comprising administering to the subject a therapeutically effective amount of the plurality of RNAs of any one of claims 1 to 6 or the nucleic acid of claim 7 or the expression vector of claim 8 or the composition of any one of claims 9 to 13.

18. A method of reducing the likelihood of long COVID in a subject infected SARS-CoV-2, comprising administering to the subject a therapeutically effective amount of the plurality of RNAs of any one of claims 1 to 6 or the nucleic acid of claim 7 or the expression vector of claim 8 or the composition of of any one of claims 9 to 13.

19. Use of a therapeutically effective amount of the plurality of RNAs of any one of claims 1 to 6 or the nucleic acid of claim 7 or the expression vector of claim 8 or the composition of any one of claims 9 to 13, in the manufacture of a medicament for treating or preventing a SARS- CoV-2 infection in a subject.

20. The plurality of RNAs of any one of claims 1 to 6 or the nucleic acid of claim 7 or the expression vector of claim 8 or the composition of any one of claims 9 to 13, for use in treating or preventing a SARS-CoV-2 infection in a subject.

21. The method of any one of claims 14 to 18 or the use of claim 19 or the plurality of RNAs or the nucleic acid or the expression vector or the composition for use according to claim 20, wherein the subject is receiving simultaneous, separate or sequential treatment for SARS-CoV-2 infection.

22. The method of any one of claims 14 to 18, 20 or 21, wherein the method comprises inhibiting expression of one or more SARS-CoV-2 genes; or the use of claim 19 or claim 21, wherein the medicament inhibits expression of one or more SARS-CoV-2 genes.