Genome-scale CRISPR‒Cas9 screen identifies novel host factors as potential therapeutic targets for SARS-CoV-2 infection

Author:

Sakai Madoka,Masuda Yoshie,Tarumoto Yusuke,Aihara Naoyuki,Tsunoda Yugo,Iwata Michiko,Kamiya Yumiko,Komorizono Ryo,Noda Takeshi,Yusa Kosuke,Tomonaga Keizo,Makino Akiko

Abstract

AbstractAlthough many host factors important for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported, the mechanisms by which the virus interacts with host cells remain elusive. Here, we identified tripartite motif containing (TRIM) 28, TRIM33, euchromatic histone lysine methyltransferase (EHMT) 1, and EHMT2 as novel proviral factors involved in SARS-CoV-2 infection by CRISPR‒Cas9 screening. We demonstrated that TRIM28 plays a role(s) in viral particle formation and that TRIM33, EHMT1, and EHMT2 are involved in viral transcription and replication using cells with suppressed gene expression. UNC0642, a compound that specifically inhibits the methyltransferase activity of EHMT1/2, strikingly suppressed SARS-CoV-2 growth in cultured cells and reduced disease severity in a hamster infection model. This study suggests that EHMT1/2 may be a novel therapeutic target for SARS-CoV-2 infection.

Publisher

Cold Spring Harbor Laboratory

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