Characterization and antiviral susceptibility of SARS-CoV-2 Omicron BA.2.
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Uraki Ryuta, Kiso Maki, Iida Shun, Imai Masaki, Takashita Emi, Kuroda Makoto, Halfmann Peter J, Loeber Samantha, Maemura Tadashi, Yamayoshi Seiya, Fujisaki Seiichiro, Wang Zhongde, Ito Mutsumi, Ujie Michiko, Iwatsuki-Horimoto Kiyoko, Furusawa Yuri, Wright Ryan, Chong Zhenlu, Ozono Seiya, Yasuhara Atsuhiro, Ueki Hiroshi, Sakai-Tagawa Yuko, Li Rong, Liu Yanan, Larson Deanna, Koga Michiko, Tsutsumi Takeya, Adachi Eisuke, Saito Makoto, Yamamoto Shinya, Hagihara Masao, Mitamura Keiko, Sato Tetsuro, Hojo Masayuki, Hattori Shin-Ichiro, Maeda Kenji, Valdez Riccardo, IASO study team, Okuda Moe, Murakami Jurika, Duong Calvin, Godbole Sucheta, Douek Daniel C, Maeda Ken, Watanabe Shinji, Gordon Aubree, Ohmagari Norio, Yotsuyanagi Hiroshi, Diamond Michael S, Hasegawa Hideki, Mitsuya Hiroaki, Suzuki Tadaki, Kawaoka Yoshihiro
Аннотация
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.