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

tetano

Editor, Senior Moderator
iScience


. 2024 Jul 8;27(8):110475.
doi: 10.1016/j.isci.2024.110475. eCollection 2024 Aug 16. Genome-scale CRISPR-Cas9 screen identifies host factors as potential therapeutic targets for SARS-CoV-2 infection

Madoka Sakai[SUP] 1 [/SUP], Yoshie Masuda[SUP] 2 [/SUP], Yusuke Tarumoto[SUP] 2 [/SUP], Naoyuki Aihara[SUP] 3 [/SUP], Yugo Tsunoda[SUP] 4 5 6 [/SUP], Michiko Iwata[SUP] 1 [/SUP], Yumiko Kamiya[SUP] 3 [/SUP], Ryo Komorizono[SUP] 1 [/SUP], Takeshi Noda[SUP] 4 5 6 [/SUP], Kosuke Yusa[SUP] 2 [/SUP], Keizo Tomonaga[SUP] 1 7 8 [/SUP], Akiko Makino[SUP] 1 7 [/SUP]



Affiliations
Abstract

Although 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 proviral factors involved in SARS-CoV-2 infection by CRISPR-Cas9 screening. Our result suggested that TRIM28 may play a role in viral particle formation and that TRIM33, EHMT1, and EHMT2 may be involved in viral transcription and replication. 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 therapeutic target for SARS-CoV-2 infection.

Keywords: Cell biology; Molecular biology; Virology.

 
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