Genome-scale CRISPR-Cas9 screen identifies host factors as potential therapeutic targets for SARS-CoV-2 infection
Madoka Sakai,
Yoshie Masuda,
Yusuke Tarumoto,
Naoyuki Aihara,
Yugo Tsunoda,
Michiko Iwata,
Yumiko Kamiya,
Ryo Komorizono,
Takeshi Noda,
Kosuke Yusa,
Keizo Tomonaga,
Akiko Makino
Affiliations
Madoka Sakai
Laboratory of RNA Viruses, Department of Virus Research, Institute for Life and Medical Sciences, Kyoto University, Kyoto 6068507, Japan
Yoshie Masuda
Laboratory of Stem Cell Genetics, Department of Biosystems Science, Institute for Life and Medical Sciences, Kyoto University, Kyoto 6068507, Japan
Yusuke Tarumoto
Laboratory of Stem Cell Genetics, Department of Biosystems Science, Institute for Life and Medical Sciences, Kyoto University, Kyoto 6068507, Japan
Naoyuki Aihara
Laboratory of Veterinary Pathology, Azabu University, Kanagawa 2520206, Japan
Yugo Tsunoda
Laboratory of Ultrastructural Virology, Department of Virus Research, Institute for Life and Medical Sciences, Kyoto University, Kyoto 6068507, Japan; Laboratory of Ultrastructural Virology, Graduate School of Biostudies, Kyoto University, Kyoto 6068507, Japan; CREST, Japan Science and Technology Agency, Saitama 1020076, Japan
Michiko Iwata
Laboratory of RNA Viruses, Department of Virus Research, Institute for Life and Medical Sciences, Kyoto University, Kyoto 6068507, Japan
Yumiko Kamiya
Laboratory of Veterinary Pathology, Azabu University, Kanagawa 2520206, Japan
Ryo Komorizono
Laboratory of RNA Viruses, Department of Virus Research, Institute for Life and Medical Sciences, Kyoto University, Kyoto 6068507, Japan
Takeshi Noda
Laboratory of Ultrastructural Virology, Department of Virus Research, Institute for Life and Medical Sciences, Kyoto University, Kyoto 6068507, Japan; Laboratory of Ultrastructural Virology, Graduate School of Biostudies, Kyoto University, Kyoto 6068507, Japan; CREST, Japan Science and Technology Agency, Saitama 1020076, Japan
Kosuke Yusa
Laboratory of Stem Cell Genetics, Department of Biosystems Science, Institute for Life and Medical Sciences, Kyoto University, Kyoto 6068507, Japan
Keizo Tomonaga
Laboratory of RNA Viruses, Department of Virus Research, Institute for Life and Medical Sciences, Kyoto University, Kyoto 6068507, Japan; Laboratory of RNA Viruses, Department of Mammalian Regulatory Network, Graduate School of Biostudies, Kyoto University, Kyoto 6068507, Japan; Department of Molecular Virology, Graduate School of Medicine, Kyoto University, Kyoto 6068507, Japan
Akiko Makino
Laboratory of RNA Viruses, Department of Virus Research, Institute for Life and Medical Sciences, Kyoto University, Kyoto 6068507, Japan; Laboratory of RNA Viruses, Department of Mammalian Regulatory Network, Graduate School of Biostudies, Kyoto University, Kyoto 6068507, Japan; Corresponding author
Summary: 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.
