Attenuated fusogenicity and pathogenicity of SARS-CoV-2 Omicron variant

Rigel Suzuki(Hokkaido University), Daichi Yamasoba(National Institute of Infectious Diseases), Izumi Kimura(National Institute of Infectious Diseases), Lei Wang(Hokkaido University), Mai Kishimoto(Hokkaido University), Jumpei Ito(National Institute of Infectious Diseases), Yuhei Morioka(Hokkaido University), Naganori Nao(Sapporo University), Hesham Nasser(Suez Canal University), Keiya Uriu(National Institute of Infectious Diseases), Yusuke Kosugi(Kyoto University), Masumi Tsuda(Hokkaido University), Yasuko Orba(Hokkaido University), Michihito Sasaki(Hokkaido University), Ryo Shimizu(Kumamoto University), Ryoko Kawabata(Hiroshima University), Kumiko Yoshimatsu(Hokkaido University), Hiroyuki Asakura(Tokyo Metropolitan Institute of Public Health), Mami Nagashima(Tokyo Metropolitan Institute of Public Health), Kenji Sadamasu(Tokyo Metropolitan Institute of Public Health), Kazuhisa Yoshimura(Tokyo Metropolitan Institute of Public Health), Mai Suganami(National Institute of Infectious Diseases), Akiko Oide(National Institute of Infectious Diseases), Mika Chiba(National Institute of Infectious Diseases), Hayato Ito(Hokkaido University), Tomokazu Tamura(Hokkaido University), Kana Tsushima(Hokkaido University), Haruko Kubo(Hokkaido University), Zannatul Ferdous(Hokkaido University), Hiromi Mouri(Hokkaido University), Miki Iida(Hokkaido University), Keiko Kasahara(Hokkaido University), Koshiro Tabata(Hokkaido University), Mariko Ishizuka(Hokkaido University), Asako Shigeno(Hokkaido University), Kenzo Tokunaga(National Institute of Infectious Diseases), Seiya Ozono(National Institute of Infectious Diseases), Isao Yoshida(Tokyo Metropolitan Institute of Public Health), So Nakagawa(Tokai University Hospital), Jiaqi Wu(Tokai University Hospital), Miyoko Takahashi(Tokai University Hospital), Atsushi Kaneda(Chiba University), M. Seki(Chiba University), Ryoji Fujiki(Chiba University), Bahityar Rahmutulla Nawai(Chiba University), Yutaka Suzuki(The University of Tokyo), Yukie Kashima(The University of Tokyo), Kazumi Abe(The University of Tokyo), Kiyomi Imamura(The University of Tokyo), Kotaro Shirakawa(Kyoto University), Akifumi Takaori‐Kondo(Kyoto University), Yasuhiro Kazuma(Kyoto University), Ryosuke Nomura(Kyoto University), Yoshihito Horisawa(Kyoto University), Kayoko Nagata(Kyoto University), Yugo Kawai(Kyoto University), Yohei Yanagida(Kyoto University), Yusuke Tashiro(Kyoto University), Otowa Takahashi(Kumamoto University), Kazuko Kitazato(Kumamoto University), Haruyo Hasebe(Kumamoto University), Chihiro Motozono(Kumamoto University), Mako Toyoda(Kumamoto University), Toong Seng Tan(Kumamoto University), Isaac Ngare(Kumamoto University), Takamasa Ueno(Kumamoto University), Akatsuki Saito(University of Miyazaki), Erika P. Butlertanaka(University of Miyazaki), Yuri Tanaka(University of Miyazaki), Nanami Morizako(University of Miyazaki), Hirofumi Sawa(Sapporo University), Terumasa Ikeda(Kumamoto University), Takashi Irie(Hiroshima University), Keita Matsuno(Hokkaido University), Shinya Tanaka(Sapporo University), Takasuke Fukuhara(Hokkaido University), Kei Sato(National Institute of Infectious Diseases)
Nature
February 1, 2022
Cited by 749Open Access
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Abstract

Abstract The emergence of the Omicron variant of SARS-CoV-2 is an urgent global health concern 1 . In this study, our statistical modelling suggests that Omicron has spread more rapidly than the Delta variant in several countries including South Africa. Cell culture experiments showed Omicron to be less fusogenic than Delta and than an ancestral strain of SARS-CoV-2. Although the spike (S) protein of Delta is efficiently cleaved into two subunits, which facilitates cell–cell fusion 2,3 , the Omicron S protein was less efficiently cleaved compared to the S proteins of Delta and ancestral SARS-CoV-2. Furthermore, in a hamster model, Omicron showed decreased lung infectivity and was less pathogenic compared to Delta and ancestral SARS-CoV-2. Our multiscale investigations reveal the virological characteristics of Omicron, including rapid growth in the human population, lower fusogenicity and attenuated pathogenicity.


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