Characterization and antiviral susceptibility of SARS-CoV-2 Omicron/BA.2
The recent emergence of SARS-CoV-2 Omicron variants possessing large numbers of mutations has raised concerns of decreased effectiveness of current vaccines, therapeutic monoclonal antibodies, and antiviral drugs for COVID-19 against these variants1,2. While the original Omicron lineage, BA.1, has b...
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| Published in | Nature |
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| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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24.02.2022
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| Abstract | The recent emergence of SARS-CoV-2 Omicron variants possessing large numbers of mutations has raised concerns of decreased effectiveness of current vaccines, therapeutic monoclonal antibodies, and antiviral drugs for COVID-19 against these variants1,2. While the original Omicron lineage, BA.1, has become dominant in many countries, BA.2 has been detected in at least 67 countries and has become dominant in the Philippines, India, and Denmark. Here, we evaluated the replicative ability and pathogenicity of an authentic infectious BA.2 isolate in immunocompetent and human ACE2 (hACE2)-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 backbone3, we observed similar infectivity and pathogenicity in mice and hamsters between BA.2 and BA.1, and less pathogenicity compared to early SARS-CoV-2 strains. We also observed a marked and significant reduction in the neutralizing activity of plasma from COVID-19 convalescent individuals and vaccine recipients against BA.2 compared to ancestral and Delta variant strains. In addition, we found that some therapeutic monoclonal antibodies (REGN10987/REGN10933, COV2-2196/COV2-2130, and S309) and antiviral drugs (molnupiravir, nirmatrelvir, and S-217622) can restrict viral infection in the respiratory organs of hamsters infected with BA.2. These findings suggest that the replication and pathogenicity of BA.2 is comparable 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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| AbstractList | The recent emergence of SARS-CoV-2 Omicron variants possessing large numbers of mutations has raised concerns of decreased effectiveness of current vaccines, therapeutic monoclonal antibodies, and antiviral drugs for COVID-19 against these variants1,2. While the original Omicron lineage, BA.1, has become dominant in many countries, BA.2 has been detected in at least 67 countries and has become dominant in the Philippines, India, and Denmark. Here, we evaluated the replicative ability and pathogenicity of an authentic infectious BA.2 isolate in immunocompetent and human ACE2 (hACE2)-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 backbone3, we observed similar infectivity and pathogenicity in mice and hamsters between BA.2 and BA.1, and less pathogenicity compared to early SARS-CoV-2 strains. We also observed a marked and significant reduction in the neutralizing activity of plasma from COVID-19 convalescent individuals and vaccine recipients against BA.2 compared to ancestral and Delta variant strains. In addition, we found that some therapeutic monoclonal antibodies (REGN10987/REGN10933, COV2-2196/COV2-2130, and S309) and antiviral drugs (molnupiravir, nirmatrelvir, and S-217622) can restrict viral infection in the respiratory organs of hamsters infected with BA.2. These findings suggest that the replication and pathogenicity of BA.2 is comparable to that of BA.1 in rodents and that several therapeutic monoclonal antibodies and antiviral compounds are effective against Omicron/BA.2 variants. |
| Author | Koga, Michiko Mitamura, Keiko Godbole, Sucheta Uraki, Ryuta Hattori, Shin-Ichiro Adachi, Eisuke Wright, Ryan Saito, Makoto Yamayoshi, Seiya Ueki, Hiroshi Iida, Shun Furusawa, Yuri Liu, Yanan Yamamoto, Shinya Imai, Masaki Halfmann, Peter Duong, Calvin Kuroda, Makoto Murakami, Jurika Ujie, Michiko Yasuhara, Atsuhiro Fujisaki, Seiichiro Sakai, Yuko Ito, Mutsumi Takashita, Emi Yotsuyanagi, Hiroshi Hagihara, Masao Hojo, Masayuki Ohmagari, Norio Maeda, Kenji Sato, Tetsuro Matsubara, Shohei Chong, Zhenlu Diamond, Michael Loeber, Samantha Li, Rong Suzuki, Tadaki Watanabe, Shinji Okuda, Moe Iwatsuki-Horimoto, Kiyoko Mitsuya, Hiroaki Kiso, Maki Wang, Zhongde Tsutsumi, Takeya Kawaoka, Yoshihiro Ozono, Seiya Maemura, Tadashi Larson, Deanna Hasegawa, Hideki Douek, Daniel |
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organization: University of Wisconsin at Madison – sequence: 8 givenname: Peter surname: Halfmann fullname: Halfmann, Peter organization: Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, USA – sequence: 9 givenname: Samantha surname: Loeber fullname: Loeber, Samantha organization: University of Wisconsin-Madison – sequence: 10 givenname: Tadashi surname: Maemura fullname: Maemura, Tadashi organization: University of Wisconsin – sequence: 11 givenname: Seiya orcidid: 0000-0001-7768-5157 surname: Yamayoshi fullname: Yamayoshi, Seiya organization: University Of Tokyo – sequence: 12 givenname: Seiichiro surname: Fujisaki fullname: Fujisaki, Seiichiro organization: National Institute of Infectious Diseases – sequence: 13 givenname: Zhongde orcidid: 0000-0003-2441-4729 surname: Wang fullname: Wang, Zhongde organization: Utah State University – sequence: 14 givenname: Mutsumi surname: Ito fullname: Ito, Mutsumi organization: University of Tokyo, Institute of Medical Science – sequence: 15 givenname: Michiko surname: Ujie fullname: Ujie, Michiko organization: Division of Virology, Institute of Medical Science, University of Tokyo – sequence: 16 givenname: Kiyoko orcidid: 0000-0002-8266-020X surname: Iwatsuki-Horimoto fullname: Iwatsuki-Horimoto, Kiyoko organization: University of Tokyo – sequence: 17 givenname: Yuri surname: Furusawa fullname: Furusawa, Yuri organization: Division of Virology, Institute of Medical Science, University of Tokyo – sequence: 18 givenname: Ryan surname: Wright fullname: Wright, Ryan organization: Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison – sequence: 19 givenname: Zhenlu surname: Chong fullname: Chong, Zhenlu organization: Washington University – sequence: 20 givenname: Seiya orcidid: 0000-0002-1764-2937 surname: Ozono fullname: Ozono, Seiya organization: National 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Agriculture and Applied Sciences – sequence: 27 givenname: Michiko surname: Koga fullname: Koga, Michiko organization: The Institute of Medical Science, the University of Tokyo – sequence: 28 givenname: Takeya surname: Tsutsumi fullname: Tsutsumi, Takeya organization: Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo – sequence: 29 givenname: Eisuke orcidid: 0000-0002-1623-873X surname: Adachi fullname: Adachi, Eisuke organization: The Institute of Medical Science, the University of Tokyo – sequence: 30 givenname: Makoto surname: Saito fullname: Saito, Makoto organization: Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo – sequence: 31 givenname: Shinya surname: Yamamoto fullname: Yamamoto, Shinya organization: Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo – sequence: 32 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| Title | Characterization and antiviral susceptibility of SARS-CoV-2 Omicron/BA.2 |
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