1. Academic Validation
  2. Virological characteristics of SARS-CoV-2-related coronaviruses dynamically circulating in Southeast Asia

Virological characteristics of SARS-CoV-2-related coronaviruses dynamically circulating in Southeast Asia

  • Cell. 2026 Jun 25;189(13):4075-4093.e25. doi: 10.1016/j.cell.2026.04.019.
Supaporn Wacharapluesadee 1 Wilaiporn Saikruang 2 Spyros Lytras 3 Kanata Matsumoto 4 Keiya Uriu 2 Alfredo Hinay Jr 2 Ziyi Guo 2 Khwankamon Rattanatumhi 5 Ananporn Supataragul 5 Sasiprapa Ninwattana 5 Nattakarn Thippamom 5 Tanawut Srisuk 5 Patarapol Maneeorn 6 Kirana Noradechanon 6 Prateep Duengkae 7 Nutthinee Sirichan 7 Yusuke Kosugi 8 Shigeru Fujita 8 Maximilian Stanley Yo 9 Ryo Matsunaga 10 Bingjie Hu 11 Lianzhao Du 11 Lei Wang 12 Masumi Tsuda 12 Yoshitaka Oda 13 Hesham Nasser 14 Kanako Terakado Kimura 15 Hiroaki Akasaka 4 Hiroyuki Asakura 16 Mami Nagashima 16 Kenji Sadamasu 16 Kazuhisa Yoshimura 16 Yuki Yamamoto 17 Tetsuharu Nagamoto 17 Takanori Asakura 18 Wataru Shihoya 4 Takao Hashiguchi 15 Terumasa Ikeda 19 Shinya Tanaka 20 Hin Chu 11 Kouhei Tsumoto 21 Osamu Nureki 4 Genotype to Phenotype Japan (G2P-Japan) Consortium Genotype to Phenotype Asia (G2P-Asia) Consortium Arnon Plianchaisuk 2 Opass Putcharoen 22 Kei Sato 23
Affiliations

Affiliations

  • 1 Thai Red Cross Emerging Infectious Diseases Clinical Center, King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. Electronic address: [email protected].
  • 2 Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  • 3 Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; MRC-University of Glasgow Centre for Virus Research, Glasgow, UK.
  • 4 Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
  • 5 Thai Red Cross Emerging Infectious Diseases Clinical Center, King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
  • 6 Department of National Parks, Wildlife and Plant Conservation, Ministry of Natural Resources and Environment, Bangkok, Thailand.
  • 7 Department of Forest Biology, Faculty of Forestry, Kasetsart University, Bangkok, Thailand.
  • 8 Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Department of Pathology, Immunology and Microbiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • 9 Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Japan.
  • 10 Department of Bioengineering, School of Engineering, The University of Tokyo, Tokyo, Japan; Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, Tokyo, Japan.
  • 11 State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
  • 12 Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, Sapporo, Japan; Institute for Chemical Reaction Design and Discovery (ICReDD), Hokkaido University, Sapporo, Japan.
  • 13 Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, Sapporo, Japan.
  • 14 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.
  • 15 Laboratory of Medical Virology, Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan.
  • 16 Tokyo Metropolitan Institute of Public Health, Tokyo, Japan.
  • 17 HiLung Inc., Kyoto, Japan.
  • 18 Laboratory of Bioregulatory Medicine, Department of Clinical Medicine, Kitasato University School of Pharmacy, Tokyo, Japan; Department of Respiratory Medicine, Kitasato University Kitasato Institute Hospital, Tokyo, Japan.
  • 19 Division of Molecular Virology and Genetics, Joint Research Center for Human Retrovirus infection, Kumamoto University, Kumamoto, Japan.
  • 20 Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, Sapporo, Japan; Institute for Chemical Reaction Design and Discovery (ICReDD), Hokkaido University, Sapporo, Japan; Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan.
  • 21 Department of Bioengineering, School of Engineering, The University of Tokyo, Tokyo, Japan; Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, Tokyo, Japan; Medical Proteomics Laboratory, the Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  • 22 Thai Red Cross Emerging Infectious Diseases Clinical Center, King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Division of Infectious Diseases, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. Electronic address: [email protected].
  • 23 Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; MRC-University of Glasgow Centre for Virus Research, Glasgow, UK; Department of Pathology, Immunology and Microbiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, 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; Collaboration Unit for Infection, Joint Research Center for Human Retrovirus infection, Kumamoto University, Kumamoto, Japan; Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore. Electronic address: [email protected].
Abstract

By sampling horseshoe bats-the reservoir hosts of SARS-CoV-2-related coronaviruses (SC2r-CoVs)-in Thailand, we present two clades of SC2r-CoVs co-circulating in the same bat population. Through a comprehensive set of experimental approaches, including cryo-electron microscopy (cryo-EM), pseudovirus and live virus assays, and hamster experiments, we characterize the virological properties of these new viruses. We show that one of the two clades discovered in this study is able to bind the human angiotensin converting enzyme 2 (ACE2) receptor; however, it exhibits reduced fusogenicity and replication in vitro and lower pathogenicity and transmissibility compared with SARS-CoV-2. Phylogeography and recombination analyses reveal a complex evolutionary history for these viruses characterized by extensive, recent geographic movement and recombination with co-circulating virus lineages. Our findings provide new insights into the diversity of SC2r-CoVs dynamically co-circulating in Southeast Asia as well as the virological characteristics of these viruses relative to SARS-CoV-2.

Keywords

Rhinolophus bats; SARS-CoV-2; bat coronavirus; pathogenicity; phylogeography; sarbecovirus; spillover; transmissibility.

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