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Broad-spectrum CRISPR-mediated inhibition of SARS-CoV-2 variants and endemic coronaviruses in vitro

Zeng, Leiping, Liu, Yanxia, Nguyenla, Xammy Huu, Abbott, Timothy R., Han, Mengting, Zhu, Yanyu, Chemparathy, Augustine, Lin, Xueqiu, Chen, Xinyi, Wang, Haifeng, and others. (2022) Broad-spectrum CRISPR-mediated inhibition of SARS-CoV-2 variants and endemic coronaviruses in vitro. Nature Communications, 13 (1). Article Number 2766. ISSN 2041-1723. (doi:10.1038/s41467-022-30546-7) (KAR id:95121)

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Official URL:
https://doi.org/10.1038/s41467-022-30546-7

Abstract

A 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.

Item Type: Article
DOI/Identification number: 10.1038/s41467-022-30546-7
Subjects: Q Science > QR Microbiology > QR355 Virology
Divisions: Divisions > Division of Natural Sciences > Medway School of Pharmacy
Depositing User: Nigel Temperton
Date Deposited: 20 May 2022 13:24 UTC
Last Modified: 23 May 2022 14:34 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/95121 (The current URI for this page, for reference purposes)
Temperton, Nigel J.: https://orcid.org/0000-0002-7978-3815
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