Broad-spectrum CRISPR-mediated inhibition of SARS-CoV-2 variants and endemic coronaviruses in vitro
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Published:2022-05-19
Issue:1
Volume:13
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Zeng LeipingORCID, Liu Yanxia, Nguyenla Xammy HuuORCID, Abbott Timothy R.ORCID, Han Mengting, Zhu YanyuORCID, Chemparathy Augustine, Lin Xueqiu, Chen Xinyi, Wang Haifeng, Rane Draven A.ORCID, Spatz Jordan M., Jain SaketORCID, Rustagi ArjunORCID, Pinsky BenjaminORCID, Zepeda Adrianna E., Kadina Anastasia P., Walker John A., Holden KevinORCID, Temperton NigelORCID, Cochran Jennifer R.ORCID, Barron Annelise E.ORCID, Connolly Michael D.ORCID, Blish Catherine A.ORCID, Lewis David B., Stanley Sarah A., La Russa Marie F., Qi Lei S.ORCID
Abstract
AbstractA major challenge in coronavirus vaccination and treatment is to counteract rapid viral evolution and mutations. Here we demonstrate that CRISPR-Cas13d offers a broad-spectrum antiviral (BSA) to inhibit many SARS-CoV-2 variants and diverse human coronavirus strains with >99% reduction of the viral titer. We show that Cas13d-mediated coronavirus inhibition is dependent on the crRNA cellular spatial colocalization with Cas13d and target viral RNA. Cas13d can significantly enhance the therapeutic effects of diverse small molecule drugs against coronaviruses for prophylaxis or treatment purposes, and the best combination reduced viral titer by over four orders of magnitude. Using lipid nanoparticle-mediated RNA delivery, we demonstrate that the Cas13d system can effectively treat infection from multiple variants of coronavirus, including Omicron SARS-CoV-2, in human primary airway epithelium air-liquid interface (ALI) cultures. Our study establishes CRISPR-Cas13 as a BSA which is highly complementary to existing vaccination and antiviral treatment strategies.
Funder
Li Ka Shing Foundation
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference73 articles.
1. Lu, L., Su, S., Yang, H. & Jiang, S. Antivirals with common targets against highly pathogenic viruses. Cell 184, 1604–1620 (2021). 2. Abdelrahman, Z., Li, M. & Wang, X. Comparative review of SARS-CoV-2, SARS-CoV, MERS-CoV, and influenza A respiratory viruses. Front. Immunol. 11, 552909 (2020). 3. Hussain, M., Galvin, H. D., Haw, T. Y., Nutsford, A. N. & Husain, M. Drug resistance in influenza A virus: the epidemiology and management. Infect. Drug Resist. 10, 121–134 (2017). 4. Sanders, J. M., Monogue, M. L., Jodlowski, T. Z. & Cutrell, J. B. Pharmacologic treatments for coronavirus disease 2019 (COVID-19). J. Am. Med. Assoc. 323, 1824–1836 (2020). 5. Cosar, B. et al. SARS-CoV-2 mutations and their viral variants. Cytokine Growth F. R. https://doi.org/10.1016/j.cytogfr.2021.06.001 (2021).
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