2. Academic Validation
  3. Characterization and antiviral susceptibility of SARS-CoV-2 Omicron BA.2

Characterization and antiviral susceptibility of SARS-CoV-2 Omicron BA.2

  • Nature. 2022 Jul;607(7917):119-127. doi: 10.1038/s41586-022-04856-1.
Ryuta Uraki # 1 2,  Maki Kiso # 1,  Shun Iida # 3,  Masaki Imai # 1 2,  Emi Takashita # 4,  Makoto Kuroda # 5,  Peter J Halfmann 5,  Samantha Loeber 6,  Tadashi Maemura 5,  Seiya Yamayoshi 1 2,  Seiichiro Fujisaki 4,  Zhongde Wang 7,  Mutsumi Ito 1,  Michiko Ujie 1 2,  Kiyoko Iwatsuki-Horimoto 1,  Yuri Furusawa 1 2 8,  Ryan Wright 5,  Zhenlu Chong 9,  Seiya Ozono 3,  Atsuhiro Yasuhara 1,  Hiroshi Ueki 1 2,  Yuko Sakai-Tagawa 1,  Rong Li 7,  Yanan Liu 7,  Deanna Larson 7,  Michiko Koga 10 11,  Takeya Tsutsumi 10 11,  Eisuke Adachi 11,  Makoto Saito 10 11,  Shinya Yamamoto 1 10,  Masao Hagihara 12,  Keiko Mitamura 13,  Tetsuro Sato 14,  Masayuki Hojo 15,  Shin-Ichiro Hattori 16,  Kenji Maeda 16,  Riccardo Valdez 17,  IASO study team,  Moe Okuda 1,  Jurika Murakami 1,  Calvin Duong 1,  Sucheta Godbole 18,  Daniel C Douek 18,  Ken Maeda 19,  Shinji Watanabe 4,  Aubree Gordon 20,  Norio Ohmagari 14,  Hiroshi Yotsuyanagi 10 11,  Michael S Diamond 9 21 22 23,  Hideki Hasegawa 4,  Hiroaki Mitsuya 16 24,  Tadaki Suzuki 3,  Yoshihiro Kawaoka 25 26 27
Affiliations

Affiliations

  • 1 Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
  • 2 The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, Japan.
  • 3 Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
  • 4 Center for Influenza and Respiratory Virus Research, National Institute of Infectious Diseases, Tokyo, Japan.
  • 5 Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.
  • 6 Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.
  • 7 Department of Animal Dairy, and Veterinary Sciences, College of Agriculture and Applied Sciences, Utah State University, Logan, UT, USA.
  • 8 Laboratory of Ultrastructural Virology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
  • 9 Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.
  • 10 Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
  • 11 Department of Infectious Diseases and Applied Immunology, IMSUT Hospital of The Institute of Medical Science, University of Tokyo, Tokyo, Japan.
  • 12 Department of Hematology, Eiju General Hospital, Tokyo, Japan.
  • 13 Division of Infection Control, Eiju General Hospital, Tokyo, Japan.
  • 14 Disease Control and Prevention Center, National Center for Global Health and Medicine Hospital, Tokyo, Japan.
  • 15 Department of Respiratory Medicine, National Center for Global Health and Medicine Hospital, Tokyo, Japan.
  • 16 Department of Refractory Viral Infections, National Center for Global Health and Medicine Research Institute, Tokyo, Japan.
  • 17 Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
  • 18 Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • 19 Department of Veterinary Science, National Institute of Infectious Diseases, Tokyo, Japan.
  • 20 Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
  • 21 Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA.
  • 22 Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO, USA.
  • 23 The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St Louis, MO, USA.
  • 24 Experimental Retrovirology Section, HIV and AIDS Malignancy Branch, National Cancer Institute, NIH, Bethesda, MD, USA.
  • 25 Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo, Japan. yoshihiro.kawaoka@wisc.edu.
  • 26 The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, Japan. yoshihiro.kawaoka@wisc.edu.
  • 27 Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA. yoshihiro.kawaoka@wisc.edu.
  • # Contributed equally.
PMID: 35576972 DOI: 10.1038/s41586-022-04856-1
Abstract

The recent emergence of SARS-CoV-2 Omicron (B.1.1.529 lineage) variants possessing numerous mutations has raised concerns of decreased effectiveness of current vaccines, therapeutic monoclonal Antibodies and Antiviral drugs for COVID-19 against these variants1,2. The original Omicron lineage, BA.1, prevailed in many countries, but more recently, BA.2 has become dominant in at least 68 countries3. Here we evaluated the replicative ability and pathogenicity of authentic infectious BA.2 isolates in immunocompetent and human ACE2-expressing mice and hamsters. In contrast to recent data with chimeric, recombinant SARS-CoV-2 strains expressing the spike proteins of BA.1 and BA.2 on an ancestral WK-521 backbone4, we observed similar infectivity and pathogenicity in mice and hamsters for BA.2 and BA.1, and less pathogenicity compared with early SARS-CoV-2 strains. We also observed a marked and significant reduction in the neutralizing activity of plasma from individuals who had recovered from COVID-19 and vaccine recipients against BA.2 compared to ancestral and Delta variant strains. In addition, we found that some therapeutic monoclonal Antibodies (REGN10987 plus REGN10933, COV2-2196 plus COV2-2130, and S309) and Antiviral drugs (molnupiravir, nirmatrelvir and S-217622) can restrict viral Infection in the respiratory organs of BA.2-infected hamsters. These findings suggest that the replication and pathogenicity of BA.2 is similar to that of BA.1 in rodents and that several therapeutic monoclonal Antibodies and Antiviral compounds are effective against Omicron BA.2 variants.

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