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

Author

Listed:
  • Ryuta Uraki

    (University of Tokyo
    National Center for Global Health and Medicine Research Institute)

  • Maki Kiso

    (University of Tokyo)

  • Shun Iida

    (National Institute of Infectious Diseases)

  • Masaki Imai

    (University of Tokyo
    National Center for Global Health and Medicine Research Institute)

  • Emi Takashita

    (National Institute of Infectious Diseases)

  • Makoto Kuroda

    (University of Wisconsin-Madison)

  • Peter J. Halfmann

    (University of Wisconsin-Madison)

  • Samantha Loeber

    (University of Wisconsin-Madison)

  • Tadashi Maemura

    (University of Wisconsin-Madison)

  • Seiya Yamayoshi

    (University of Tokyo
    National Center for Global Health and Medicine Research Institute)

  • Seiichiro Fujisaki

    (National Institute of Infectious Diseases)

  • Zhongde Wang

    (Utah State University)

  • Mutsumi Ito

    (University of Tokyo)

  • Michiko Ujie

    (University of Tokyo
    National Center for Global Health and Medicine Research Institute)

  • Kiyoko Iwatsuki-Horimoto

    (University of Tokyo)

  • Yuri Furusawa

    (University of Tokyo
    National Center for Global Health and Medicine Research Institute
    Kyoto University)

  • Ryan Wright

    (University of Wisconsin-Madison)

  • Zhenlu Chong

    (Washington University School of Medicine)

  • Seiya Ozono

    (National Institute of Infectious Diseases)

  • Atsuhiro Yasuhara

    (University of Tokyo)

  • Hiroshi Ueki

    (University of Tokyo
    National Center for Global Health and Medicine Research Institute)

  • Yuko Sakai-Tagawa

    (University of Tokyo)

  • Rong Li

    (Utah State University)

  • Yanan Liu

    (Utah State University)

  • Deanna Larson

    (Utah State University)

  • Michiko Koga

    (University of Tokyo
    University of Tokyo)

  • Takeya Tsutsumi

    (University of Tokyo
    University of Tokyo)

  • Eisuke Adachi

    (University of Tokyo)

  • Makoto Saito

    (University of Tokyo
    University of Tokyo)

  • Shinya Yamamoto

    (University of Tokyo
    University of Tokyo)

  • Masao Hagihara

    (Eiju General Hospital)

  • Keiko Mitamura

    (Eiju General Hospital)

  • Tetsuro Sato

    (National Center for Global Health and Medicine Hospital)

  • Masayuki Hojo

    (National Center for Global Health and Medicine Hospital)

  • Shin-ichiro Hattori

    (National Center for Global Health and Medicine Research Institute)

  • Kenji Maeda

    (National Center for Global Health and Medicine Research Institute)

  • Riccardo Valdez

    (University of Michigan)

  • Moe Okuda

    (University of Tokyo)

  • Jurika Murakami

    (University of Tokyo)

  • Calvin Duong

    (University of Tokyo)

  • Sucheta Godbole

    (National Institutes of Health)

  • Daniel C. Douek

    (National Institutes of Health)

  • Ken Maeda

    (National Institute of Infectious Diseases)

  • Shinji Watanabe

    (National Institute of Infectious Diseases)

  • Aubree Gordon

    (University of Michigan)

  • Norio Ohmagari

    (National Center for Global Health and Medicine Hospital)

  • Hiroshi Yotsuyanagi

    (University of Tokyo
    University of Tokyo)

  • Michael S. Diamond

    (Washington University School of Medicine
    Washington University School of Medicine
    Washington University School of Medicine
    Washington University School of Medicine)

  • Hideki Hasegawa

    (National Institute of Infectious Diseases)

  • Hiroaki Mitsuya

    (National Center for Global Health and Medicine Research Institute
    NIH)

  • Tadaki Suzuki

    (National Institute of Infectious Diseases)

  • Yoshihiro Kawaoka

    (University of Tokyo
    National Center for Global Health and Medicine Research Institute
    University of Wisconsin-Madison)

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.

Suggested Citation

  • Ryuta Uraki & Maki Kiso & Shun Iida & Masaki Imai & Emi Takashita & Makoto Kuroda & Peter J. Halfmann & Samantha Loeber & Tadashi Maemura & Seiya Yamayoshi & Seiichiro Fujisaki & Zhongde Wang & Mutsum, 2022. "Characterization and antiviral susceptibility of SARS-CoV-2 Omicron BA.2," Nature, Nature, vol. 607(7917), pages 119-127, July.
    • Handle: RePEc:nat:nature:v:607:y:2022:i:7917:d:10.1038_s41586-022-04856-1
    DOI: 10.1038/s41586-022-04856-1
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    Citations

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    Cited by:

    1. Taha Y. Taha & Irene P. Chen & Jennifer M. Hayashi & Takako Tabata & Keith Walcott & Gabriella R. Kimmerly & Abdullah M. Syed & Alison Ciling & Rahul K. Suryawanshi & Hannah S. Martin & Bryan H. Bach , 2023. "Rapid assembly of SARS-CoV-2 genomes reveals attenuation of the Omicron BA.1 variant through NSP6," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Ryuta Uraki & Shun Iida & Peter J. Halfmann & Seiya Yamayoshi & Yuichiro Hirata & Kiyoko Iwatsuki-Horimoto & Maki Kiso & Mutsumi Ito & Yuri Furusawa & Hiroshi Ueki & Yuko Sakai-Tagawa & Makoto Kuroda , 2023. "Characterization of SARS-CoV-2 Omicron BA.2.75 clinical isolates," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    3. Nobuyo Higashi-Kuwata & Kohei Tsuji & Hironori Hayashi & Haydar Bulut & Maki Kiso & Masaki Imai & Hiromi Ogata-Aoki & Takahiro Ishii & Takuya Kobayakawa & Kenta Nakano & Nobutoki Takamune & Naoki Kish, 2023. "Identification of SARS-CoV-2 Mpro inhibitors containing P1’ 4-fluorobenzothiazole moiety highly active against SARS-CoV-2," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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