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Virological characteristics of the SARS-CoV-2 Omicron BA.2 subvariants, including BA.4 and BA.5.

Izumi Kimura | Daichi Yamasoba | Tomokazu Tamura | Naganori Nao | Tateki Suzuki | Yoshitaka Oda | Shuya Mitoma | Jumpei Ito | Hesham Nasser | Jiri Zahradnik | Keiya Uriu | Shigeru Fujita | Yusuke Kosugi | Lei Wang | Masumi Tsuda | Mai Kishimoto | Hayato Ito | Rigel Suzuki | Ryo Shimizu | Mst Monira Begum | Kumiko Yoshimatsu | Kanako Terakado Kimura | Jiei Sasaki | Kaori Sasaki-Tabata | Yuki Yamamoto | Tetsuharu Nagamoto | Jun Kanamune | Kouji Kobiyama | Hiroyuki Asakura | Mami Nagashima | Kenji Sadamasu | Kazuhisa Yoshimura | Kotaro Shirakawa | Akifumi Takaori-Kondo | Jin Kuramochi | Gideon Schreiber | Ken J Ishii | Genotype to Phenotype Japan (G2P-Japan) Consortium | Takao Hashiguchi | Terumasa Ikeda | Akatsuki Saito | Takasuke Fukuhara | Shinya Tanaka | Keita Matsuno | Kei Sato
Cell | 2022

After the global spread of the SARS-CoV-2 Omicron BA.2, some BA.2 subvariants, including BA.2.9.1, BA.2.11, BA.2.12.1, BA.4, and BA.5, emerged in multiple countries. Our statistical analysis showed that the effective reproduction numbers of these BA.2 subvariants are greater than that of the original BA.2. Neutralization experiments revealed that the immunity induced by BA.1/2 infections is less effective against BA.4/5. Cell culture experiments showed that BA.2.12.1 and BA.4/5 replicate more efficiently in human alveolar epithelial cells than BA.2, and particularly, BA.4/5 is more fusogenic than BA.2. We further provided the structure of the BA.4/5 spike receptor-binding domain that binds to human ACE2 and considered how the substitutions in the BA.4/5 spike play roles in ACE2 binding and immune evasion. Moreover, experiments using hamsters suggested that BA.4/5 is more pathogenic than BA.2. Our multiscale investigations suggest that the risk of BA.2 subvariants, particularly BA.4/5, to global health is greater than that of original BA.2.

Pubmed ID: 36198317

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