In late 2023, several SARS-CoV-2 XBB descendants, notably EG.5.1, were predominant worldwide. However, a distinct SARS-CoV-2 lineage, the BA.2.86 variant, also emerged. BA.2.86 is phylogenetically distinct from other Omicron sublineages, accumulating over 30 amino acid mutations in its spike protein. Here, we examined the virological characteristics of the BA.2.86 variant. Our epidemic dynamics modeling suggested that the relative reproduction number of BA.2.86 is significantly higher than that of EG.5.1. Additionally, four clinically available antivirals were effective against BA.2.86. Although the fusogenicity of BA.2.86 spike is similar to that of the parental BA.2 spike, the intrinsic pathogenicity of BA.2.86 in hamsters was significantly lower than that of BA.2. Since the growth kinetics of BA.2.86 are significantly lower than those of BA.2 both in vitro and in vivo, the attenuated pathogenicity of BA.2.86 is likely due to its decreased replication capacity. These findings uncover the features of BA.2.86, providing insights for control and treatment.

1st Medical Faculty at Biocev Charles University Vestec Prague Czechia

1st Medical Faculty at Biocev Charles University Vestec Prague Czechia; Facultad de Ciencias de la Salud Universidad Cardenal Herrera CEU CEU Universities Valencia Spain

Center for iPS Cell Research and Application Kyoto University Kyoto Japan

Center for iPS Cell Research and Application Kyoto University Kyoto Japan; AMED CREST Japan Agency for Medical Research and Development Tokyo Japan

Department of Cancer Pathology Faculty of Medicine Hokkaido University Sapporo Japan

Department of Cancer Pathology Faculty of Medicine Hokkaido University Sapporo Japan; Institute for Chemical Reaction Design and Discovery Hokkaido University Sapporo Japan

Department of Microbiology and Immunology Faculty of Medicine Hokkaido University Sapporo Japan

Department of Microbiology and Immunology Faculty of Medicine Hokkaido University Sapporo Japan; Institute for Vaccine Research and Development Hokkaido University Sapporo Japan

Department of Microbiology and Immunology Faculty of Medicine Hokkaido University Sapporo Japan; Institute for Vaccine Research and Development Hokkaido University Sapporo Japan; One Health Research Center Hokkaido University Sapporo Japan; Graduate School of Medicine Hokkaido University Sapporo Japan; School of Medicine Hokkaido University Sapporo Japan; Institute for the Advancement of Higher Education Hokkaido University Sapporo Japan

Department of Microbiology and Immunology Faculty of Medicine Hokkaido University Sapporo Japan; Institute for Vaccine Research and Development Hokkaido University Sapporo Japan; One Health Research Center Hokkaido University Sapporo Japan; Graduate School of Medicine Hokkaido University Sapporo Japan; School of Medicine Hokkaido University Sapporo Japan; Institute for the Advancement of Higher Education Hokkaido University Sapporo Japan; AMED CREST Japan Agency for Medical Research and Development Tokyo Japan; Laboratory of Virus Control Research Institute for Microbial Diseases Osaka University Suita Japan

Department of Veterinary Science Faculty of Agriculture University of Miyazaki Miyazaki Japan

Department of Veterinary Science Faculty of Agriculture University of Miyazaki Miyazaki Japan; Center for Animal Disease Control University of Miyazaki Miyazaki Japan; Graduate School of Medicine and Veterinary Medicine University of Miyazaki Miyazaki Japan

Division of Molecular Virology and Genetics Joint Research Center for Human Retrovirus Infection Kumamoto University Kumamoto Japan

Division of Molecular Virology and Genetics Joint Research Center for Human Retrovirus Infection Kumamoto University Kumamoto Japan; Faculty of Medicine Suez Canal University Ismailia Egypt

Division of Risk Analysis and Management International Institute for Zoonosis Control Hokkaido University Sapporo Japan

Division of Systems Virology Department of Microbiology and Immunology The Institute of Medical Science The University of Tokyo Tokyo Japan

Division of Systems Virology Department of Microbiology and Immunology The Institute of Medical Science The University of Tokyo Tokyo Japan; Faculty of Natural Science Imperial College London London UK

Division of Systems Virology Department of Microbiology and Immunology The Institute of Medical Science The University of Tokyo Tokyo Japan; Graduate School of Frontier Sciences The University of Tokyo Kashiwa Japan

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

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; Graduate School of Frontier Sciences The University of Tokyo Kashiwa Japan; International Vaccine Design Center The Institute of Medical Science The University of Tokyo Tokyo Japan; CREST Japan Science and Technology Agency Kawaguchi Japan; International Research Center for Infectious Diseases The Institute of Medical Science The University of Tokyo Tokyo Japan; Collaboration Unit for Infection Joint Research Center for Human Retrovirus Infection Kumamoto University Kumamoto Japan

Division of Systems Virology Department of Microbiology and Immunology The Institute of Medical Science The University of Tokyo Tokyo Japan; Indonesia International Institute for Life Sciences Jakarta Indonesia

Division of Systems Virology Department of Microbiology and Immunology 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 Biomedical and Health Sciences Hiroshima University Hiroshima Japan

Institute for Vaccine Research and Development Hokkaido University Sapporo Japan; One Health Research Center Hokkaido University Sapporo Japan; Division of International Research Promotion International Institute for Zoonosis Control Hokkaido University Sapporo Japan

Institute for Vaccine Research and Development Hokkaido University Sapporo Japan; One Health Research Center Hokkaido University Sapporo Japan; Division of Risk Analysis and Management International Institute for Zoonosis Control Hokkaido University Sapporo Japan; International Collaboration Unit International Institute for Zoonosis Control Hokkaido University Sapporo Japan

Tokyo Metropolitan Institute of Public Health Tokyo Japan

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