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Evitar: designing anti-viral RNA therapies against future RNA viruses.

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MOTIVATION The COVID-19 pandemic has highlighted the threat of emerging respiratory viruses and has exposed the lack of availability of off-the-shelf therapeutics against new RNA viruses. Previous research has established… Click to show full abstract

MOTIVATION The COVID-19 pandemic has highlighted the threat of emerging respiratory viruses and has exposed the lack of availability of off-the-shelf therapeutics against new RNA viruses. Previous research has established the potential that siRNAs and RNA-targeting CRISPR have in combating known RNA viruses. However, the feasibility and tools for designing anti-viral RNA therapeutics against future RNA viruses have not yet been established. RESULTS We develop the Evitar (Emerging-Virus-Targeting RNA) pipeline for designing anti-viral siRNAs and CRISPR Cas13a guide RNA (gRNA) sequences. Within Evitar, we develop Greedy Algorithm with Redundancy (GAR) and Similarity-weighted Greedy Algorithm with Redundancy (SGAR) to enhance the performance. Time simulations using known coronavirus genomes deposited as early as 10 years prior to the COVID-19 outbreak show that at least three SARS-CoV-2-targeting siRNAs are among the top 30 pre-designed siRNAs. Additionally, among the top 19 pre-designed gRNAs, there are three SARS-CoV-2-targeting Cas13a gRNAs that could be predicted using information from 2011. Before-the-outbreak design is also possible against the MERS-CoV virus and the 2009-H1N1 swine flu virus. Designed siRNAs are further shown to suppress SARS-CoV-2 viral sequences using in vitro reporter assays. Our results support the utility of Evitar to pre-design anti-viral siRNAs/gRNAs against future viruses. Therefore, we propose the development of a collection consisting of roughly 30 pre-designed, safety-tested, and off-the-shelf siRNA/CRISPR therapeutics that could accelerate responses to future RNA virus outbreaks. AVAILABILITY Codes are available at GitHub (https://github.com/dingyaozhang/Evitar). SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.

Keywords: viral rna; rna; anti viral; designing anti; future rna; rna viruses

Journal Title: Bioinformatics
Year Published: 2022

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