iScience (Dec 2022)
The SARS-CoV-2 spike S375F mutation characterizes the Omicron BA.1 variant
- Izumi Kimura,
- Daichi Yamasoba,
- Hesham Nasser,
- Jiri Zahradnik,
- Yusuke Kosugi,
- Jiaqi Wu,
- Kayoko Nagata,
- Keiya Uriu,
- Yuri L. Tanaka,
- Jumpei Ito,
- Ryo Shimizu,
- Toong Seng Tan,
- Erika P. Butlertanaka,
- Hiroyuki Asakura,
- Kenji Sadamasu,
- Kazuhisa Yoshimura,
- Takamasa Ueno,
- Akifumi Takaori-Kondo,
- Gideon Schreiber,
- Mako Toyoda,
- Kotaro Shirakawa,
- Takashi Irie,
- Akatsuki Saito,
- So Nakagawa,
- Terumasa Ikeda,
- Kei Sato
Affiliations
- Izumi Kimura
- Division of Systems Virology, Department of Microbiology and Immunology, the Institute of Medical Science, the University of Tokyo, Tokyo 1088639, Japan
- Daichi Yamasoba
- Division of Systems Virology, Department of Microbiology and Immunology, the Institute of Medical Science, the University of Tokyo, Tokyo 1088639, Japan; Faculty of Medicine, Kobe University, Kobe 6500017, Japan
- Hesham Nasser
- Division of Molecular Virology and Genetics, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto 8600811, Japan; Department of Clinical Pathology, Faculty of Medicine, Suez Canal University, Ismailia 41511, Egypt
- Jiri Zahradnik
- Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 76100, Israel
- Yusuke Kosugi
- Division of Systems Virology, Department of Microbiology and Immunology, the Institute of Medical Science, the University of Tokyo, Tokyo 1088639, Japan; Graduate School of Medicine, the University of Tokyo, Tokyo 1130033, Japan
- Jiaqi Wu
- Department of Molecular Life Science, Tokai University School of Medicine, Isehara 2591193, Japan; CREST, Japan Science and Technology Agency, Kawaguchi 3220012, Japan
- Kayoko Nagata
- Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto 6068507, Japan
- Keiya Uriu
- Division of Systems Virology, Department of Microbiology and Immunology, the Institute of Medical Science, the University of Tokyo, Tokyo 1088639, Japan; Graduate School of Medicine, the University of Tokyo, Tokyo 1130033, Japan
- Yuri L. Tanaka
- Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki, Miyazaki 8892192, Japan
- Jumpei Ito
- Division of Systems Virology, Department of Microbiology and Immunology, the Institute of Medical Science, the University of Tokyo, Tokyo 1088639, Japan
- Ryo Shimizu
- Division of Molecular Virology and Genetics, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto 8600811, Japan
- Toong Seng Tan
- Division of Infection and Immunity, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto 8600811, Japan
- Erika P. Butlertanaka
- Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki, Miyazaki 8892192, Japan
- Hiroyuki Asakura
- Tokyo Metropolitan Institute of Public Health, Tokyo 1690073, Japan
- Kenji Sadamasu
- Tokyo Metropolitan Institute of Public Health, Tokyo 1690073, Japan
- Kazuhisa Yoshimura
- Tokyo Metropolitan Institute of Public Health, Tokyo 1690073, Japan
- Takamasa Ueno
- Division of Infection and Immunity, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto 8600811, Japan
- Akifumi Takaori-Kondo
- Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto 6068507, Japan
- Gideon Schreiber
- Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 76100, Israel
- Mako Toyoda
- Division of Infection and Immunity, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto 8600811, Japan
- Kotaro Shirakawa
- Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto 6068507, Japan
- Takashi Irie
- Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 7398511, Japan
- Akatsuki Saito
- Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki, Miyazaki 8892192, Japan; Center for Animal Disease Control, University of Miyazaki, Miyazaki 8892192, Japan; Graduate School of Medicine and Veterinary Medicine, University of Miyazaki, Miyazaki 8891692, Japan; Corresponding author
- So Nakagawa
- Department of Molecular Life Science, Tokai University School of Medicine, Isehara 2591193, Japan; CREST, Japan Science and Technology Agency, Kawaguchi 3220012, Japan; Corresponding author
- Terumasa Ikeda
- Division of Molecular Virology and Genetics, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto 8600811, Japan; Corresponding author
- Kei Sato
- Division of Systems Virology, Department of Microbiology and Immunology, the Institute of Medical Science, the University of Tokyo, Tokyo 1088639, Japan; Graduate School of Medicine, the University of Tokyo, Tokyo 1130033, Japan; CREST, Japan Science and Technology Agency, Kawaguchi 3220012, Japan; International Research Center for Infectious Diseases, the Institute of Medical Science, the University of Tokyo, Tokyo 1088639, Japan; International Vaccine Design Center, the Institute of Medical Science, the University of Tokyo, Tokyo 1088639, Japan; Graduate School of Frontier Sciences, the University of Tokyo, Kashiwa 2778561, Japan; Collaboration Unit for Infection, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto 8600811, Japan; Corresponding author
- Journal volume & issue
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Vol. 25,
no. 12
p. 105720
Abstract
Summary: Recent studies have revealed the unique virological characteristics of Omicron, particularly those of its spike protein, such as less cleavage efficacy in cells, reduced ACE2 binding affinity, and poor fusogenicity. However, it remains unclear which mutation(s) determine these three virological characteristics of Omicron spike. Here, we show that these characteristics of the Omicron spike protein are determined by its receptor-binding domain. Of interest, molecular phylogenetic analysis revealed that acquisition of the spike S375F mutation was closely associated with the explosive spread of Omicron in the human population. We further elucidated that the F375 residue forms an interprotomer pi-pi interaction with the H505 residue of another protomer in the spike trimer, conferring the attenuated cleavage efficiency and fusogenicity of Omicron spike. Our data shed light on the evolutionary events underlying the emergence of Omicron at the molecular level.
