Summary The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and variants has led to significant mortality. We recently reported that an RNA-targeting CRISPR-Cas13 system, called prophylactic antiviral CRISPR in human cells (PAC-MAN), offered an antiviral strategy against SARS-CoV-2 and influenza A virus. Here, we expand in silico analysis to use PAC-MAN to target a broad spectrum of human- or livestock-infectious RNA viruses with high specificity, coverage, and predicted efficiency. Our analysis reveals that a minimal set of 14 CRISPR RNAs (crRNAs) is able to target >90% of human-infectious viruses across 10 RNA virus families. We predict that a set of 5 experimentally validated crRNAs can target new SARS-CoV-2 variant sequences with zero mismatches. We also build an online resource (crispr-pacman.stanford.edu) to support community use of CRISPR-Cas13 for broad-spectrum RNA virus targeting. Our work provides a new bioinformatic resource for using CRISPR-Cas13 to target diverse RNA viruses to facilitate the development of CRISPR-based antivirals. Graphical abstract Highlights A web resource for using CRISPR-Cas13 to target broad RNA virus families A bioinformatic tool to analyze efficiency and specificity of virus-targeting crRNAs A minipool of crRNAs can target 90% of human-infectious RNA viruses Validated crRNAs are predicted to target newly emerging SARS-CoV-2 variants Lin et al. develop a bioinformatic tool and an online resource for using CRISPR-Cas13 to target diverse human-infecting RNA viruses (10 families and 24,096 strains) with high efficiency and specificity.
【저자키워드】 COVID-19, SARS-CoV-2, Antiviral, Infectious disease, CRISPR, Cas13, RNA virus, PAC-MAN,