1. Development of CRISPR as an Antiviral Strategy to Combat SARS-CoV-2 and Influenza.
- Author
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Abbott TR, Dhamdhere G, Liu Y, Lin X, Goudy L, Zeng L, Chemparathy A, Chmura S, Heaton NS, Debs R, Pande T, Endy D, La Russa MF, Lewis DB, and Qi LS
- Subjects
- A549 Cells, Antibiotic Prophylaxis methods, Base Sequence, Betacoronavirus genetics, Betacoronavirus growth & development, COVID-19, Clustered Regularly Interspaced Short Palindromic Repeats, Computer Simulation, Conserved Sequence, Coronavirus drug effects, Coronavirus genetics, Coronavirus growth & development, Coronavirus Infections drug therapy, Coronavirus Nucleocapsid Proteins, Coronavirus RNA-Dependent RNA Polymerase, Epithelial Cells virology, Humans, Influenza A Virus, H1N1 Subtype genetics, Influenza A Virus, H1N1 Subtype growth & development, Lung pathology, Lung virology, Nucleocapsid Proteins genetics, Pandemics, Phosphoproteins, Phylogeny, Pneumonia, Viral drug therapy, RNA-Dependent RNA Polymerase genetics, SARS-CoV-2, Viral Nonstructural Proteins genetics, Antiviral Agents pharmacology, Betacoronavirus drug effects, CRISPR-Cas Systems, Influenza A Virus, H1N1 Subtype drug effects, RNA, Viral antagonists & inhibitors
- Abstract
The coronavirus disease 2019 (COVID-19) pandemic, caused by the SARS-CoV-2 virus, has highlighted the need for antiviral approaches that can target emerging viruses with no effective vaccines or pharmaceuticals. Here, we demonstrate a CRISPR-Cas13-based strategy, PAC-MAN (prophylactic antiviral CRISPR in human cells), for viral inhibition that can effectively degrade RNA from SARS-CoV-2 sequences and live influenza A virus (IAV) in human lung epithelial cells. We designed and screened CRISPR RNAs (crRNAs) targeting conserved viral regions and identified functional crRNAs targeting SARS-CoV-2. This approach effectively reduced H1N1 IAV load in respiratory epithelial cells. Our bioinformatic analysis showed that a group of only six crRNAs can target more than 90% of all coronaviruses. With the development of a safe and effective system for respiratory tract delivery, PAC-MAN has the potential to become an important pan-coronavirus inhibition strategy., Competing Interests: Declaration of Interests The authors have filed provisional patents via Stanford University related to this work., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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