Virological characteristics of the SARS-CoV-2 Omicron BA.2.75 variant

Akatsuki Saito; Tomokazu Tamura; Jiri Zahradnik; Sayaka Deguchi; Koshiro Tabata; Yuki Anraku; Izumi Kimura; Jumpei Ito; Daichi Yamasoba; Hesham Nasser; Mako Toyoda; Kayoko Nagata; Keiya Uriu; Yusuke Kosugi; Shigeru Fujita; Maya Shofa; Mst Monira Begum; Ryo Shimizu; Yoshitaka Oda; Rigel Suzuki; Hayato Ito; Naganori Nao; Lei Wang; Masumi Tsuda; Kumiko Yoshimatsu; Jin Kuramochi; Shunsuke Kita; Kaori Sasaki-Tabata; Hideo Fukuhara; Katsumi Maenaka; Yuki Yamamoto; Tetsuharu Nagamoto; Hiroyuki Asakura; Mami Nagashima; Kenji Sadamasu; Kazuhisa Yoshimura; Takamasa Ueno; Gideon Schreiber; Akifumi Takaori-Kondo; Genotype to Phenotype Japan (G2P-Japan) Consortium; Kotaro Shirakawa; Hirofumi Sawa; Takashi Irie; Takao Hashiguchi; Kazuo Takayama; Keita Matsuno; Shinya Tanaka; Terumasa Ikeda; Takasuke Fukuhara; Kei Sato

doi:10.1016/j.chom.2022.10.003

Virological characteristics of the SARS-CoV-2 Omicron BA.2.75 variant

Cell Host Microbe. 2022 Nov 9;30(11):1540-1555.e15. doi: 10.1016/j.chom.2022.10.003. Epub 2022 Oct 18.

Authors

Akatsuki Saito¹, Tomokazu Tamura², Jiri Zahradnik³, Sayaka Deguchi⁴, Koshiro Tabata⁵, Yuki Anraku⁶, Izumi Kimura⁷, Jumpei Ito⁷, Daichi Yamasoba⁸, Hesham Nasser⁹, Mako Toyoda¹⁰, Kayoko Nagata¹¹, Keiya Uriu¹², Yusuke Kosugi¹², Shigeru Fujita¹², Maya Shofa¹³, Mst Monira Begum¹⁴, Ryo Shimizu¹⁴, Yoshitaka Oda¹⁵, Rigel Suzuki², Hayato Ito², Naganori Nao¹⁶, Lei Wang¹⁷, Masumi Tsuda¹⁷, Kumiko Yoshimatsu¹⁸, Jin Kuramochi¹⁹, Shunsuke Kita⁶, Kaori Sasaki-Tabata²⁰, Hideo Fukuhara²¹, Katsumi Maenaka²², Yuki Yamamoto²³, Tetsuharu Nagamoto²³, Hiroyuki Asakura²⁴, Mami Nagashima²⁴, Kenji Sadamasu²⁴, Kazuhisa Yoshimura²⁴, Takamasa Ueno¹⁰, Gideon Schreiber²⁵, Akifumi Takaori-Kondo¹¹; Genotype to Phenotype Japan (G2P-Japan) Consortium; Kotaro Shirakawa¹¹, Hirofumi Sawa²⁶, Takashi Irie²⁷, Takao Hashiguchi²⁸, Kazuo Takayama²⁹, Keita Matsuno³⁰, Shinya Tanaka³¹, Terumasa Ikeda³², Takasuke Fukuhara³³, Kei Sato³⁴

Affiliations

¹ Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki, Miyazaki, Japan; Graduate School of Medicine and Veterinary Medicine, University of Miyazaki, Miyazaki, Japan; Center for Animal Disease Control, University of Miyazaki, Miyazaki, Japan.
² Department of Microbiology and Immunology, Faculty of Medicine, Hokkaido University, Sapporo, Japan.
³ Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel; First Medical Faculty at Biocev, Charles University, Vestec, Prague, Czechia.
⁴ Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
⁵ Division of Molecular Pathobiology, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan.
⁶ Laboratory of Biomolecular Science and Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
⁷ Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
⁸ Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Faculty of Medicine, Kobe University, Kobe, Japan.
⁹ Division of Molecular Virology and Genetics, Joint Research Center for Human Retrovirus infection, Kumamoto University, Kumamoto, Japan; Department of Clinical Pathology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
¹⁰ Division of Infection and immunity, Joint Research Center for Human Retrovirus infection, Kumamoto University, Kumamoto, Japan.
¹¹ Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
¹² Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
¹³ Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki, Miyazaki, Japan; Graduate School of Medicine and Veterinary Medicine, University of Miyazaki, Miyazaki, Japan.
¹⁴ Division of Molecular Virology and Genetics, Joint Research Center for Human Retrovirus infection, Kumamoto University, Kumamoto, Japan.
¹⁵ Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, Sapporo, Japan.
¹⁶ Division of International Research Promotion, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan.
¹⁷ Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, Sapporo, Japan; Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, Sapporo, Japan.
¹⁸ Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
¹⁹ Interpark Kuramochi Clinic, Utsunomiya, Japan; Department of Global Health Promotion, Tokyo Medical and Dental University, Tokyo, Japan.
²⁰ Department of Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
²¹ Global Station for Biosurfaces and Drug Discovery, Hokkaido University, Sapporo, Japan; Division of Pathogen Structure, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan.
²² Laboratory of Biomolecular Science and Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan; Global Station for Biosurfaces and Drug Discovery, Hokkaido University, Sapporo, Japan; Division of Pathogen Structure, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan.
²³ HiLung Inc., Kyoto, Japan.
²⁴ Tokyo Metropolitan Institute of Public Health, Tokyo, Japan.
²⁵ Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel.
²⁶ Division of Molecular Pathobiology, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan; Division of International Research Promotion, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan; One Health Research Center, Hokkaido University, Sapporo, Japan.
²⁷ Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
²⁸ Laboratory of Medical Virology, Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan.
²⁹ Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan; AMED-CREST, Japan Agency for Medical Research and Development (AMED), Tokyo, Japan.
³⁰ One Health Research Center, Hokkaido University, Sapporo, Japan; International Collaboration Unit, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan; Division of Risk Analysis and Management, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan.
³¹ Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, Sapporo, Japan; Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, Sapporo, Japan. Electronic address: tanaka@med.hokudai.ac.jp.
³² Division of Molecular Virology and Genetics, Joint Research Center for Human Retrovirus infection, Kumamoto University, Kumamoto, Japan. Electronic address: ikedat@kumamoto-u.ac.jp.
³³ Department of Microbiology and Immunology, Faculty of Medicine, Hokkaido University, Sapporo, Japan; Laboratory of Virus Control, Research Institute for Microbial Diseases, Osaka University, Suita, Japan. Electronic address: fukut@pop.med.hokudai.ac.jp.
³⁴ Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; International Vaccine Design Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Japan; Collaboration Unit for Infection, Joint Research Center for Human Retrovirus infection, Kumamoto University, Kumamoto, Japan; CREST, Japan Science and Technology Agency, Kawaguchi, Japan. Electronic address: keisato@g.ecc.u-tokyo.ac.jp.

Abstract

The SARS-CoV-2 Omicron BA.2.75 variant emerged in May 2022. BA.2.75 is a BA.2 descendant but is phylogenetically distinct from BA.5, the currently predominant BA.2 descendant. Here, we show that BA.2.75 has a greater effective reproduction number and different immunogenicity profile than BA.5. We determined the sensitivity of BA.2.75 to vaccinee and convalescent sera as well as a panel of clinically available antiviral drugs and antibodies. Antiviral drugs largely retained potency, but antibody sensitivity varied depending on several key BA.2.75-specific substitutions. The BA.2.75 spike exhibited a profoundly higher affinity for its human receptor, ACE2. Additionally, the fusogenicity, growth efficiency in human alveolar epithelial cells, and intrinsic pathogenicity in hamsters of BA.2.75 were greater than those of BA.2. Our multilevel investigations suggest that BA.2.75 acquired virological properties independent of BA.5, and the potential risk of BA.2.75 to global health is greater than that of BA.5.

Keywords: BA.2.75; COVID-19; Omicron; SARS-CoV-2; antiviral drug resistance; immune resistance; pathogenicity; transmissibility.

MeSH terms

Antibodies, Neutralizing
Antibodies, Viral
Antiviral Agents / pharmacology
Antiviral Agents / therapeutic use
COVID-19 Serotherapy
COVID-19*
Humans
SARS-CoV-2* / genetics
Spike Glycoprotein, Coronavirus / genetics

Substances

Antibodies, Neutralizing
Antibodies, Viral
Antiviral Agents
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2

Supplementary concepts

SARS-CoV-2 variants