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

Author:

Suzuki Rigel,Yamasoba Daichi,Kimura Izumi,Wang LeiORCID,Kishimoto Mai,Ito JumpeiORCID,Morioka Yuhei,Nao Naganori,Nasser HeshamORCID,Uriu Keiya,Kosugi Yusuke,Tsuda MasumiORCID,Orba YasukoORCID,Sasaki MichihitoORCID,Shimizu Ryo,Kawabata Ryoko,Yoshimatsu KumikoORCID,Asakura HiroyukiORCID,Nagashima MamiORCID,Sadamasu KenjiORCID,Yoshimura Kazuhisa,Suganami Mai,Oide Akiko,Chiba Mika,Ito Hayato,Tamura Tomokazu,Tsushima Kana,Kubo Haruko,Ferdous Zannatul,Mouri Hiromi,Iida Miki,Kasahara Keiko,Tabata Koshiro,Ishizuka Mariko,Shigeno Asako,Tokunaga Kenzo,Ozono Seiya,Yoshida Isao,Nakagawa So,Wu Jiaqi,Takahashi Miyoko,Kaneda Atsushi,Seki Motoaki,Fujiki Ryoji,Nawai Bahityar Rahmutulla,Suzuki Yutaka,Kashima Yukie,Abe Kazumi,Imamura Kiyomi,Shirakawa Kotaro,Takaori-Kondo Akifumi,Kazuma Yasuhiro,Nomura Ryosuke,Horisawa Yoshihito,Nagata Kayoko,Kawai Yugo,Yanagida Yohei,Tashiro Yusuke,Takahashi Otowa,Kitazato Kazuko,Hasebe Haruyo,Motozono Chihiro,Toyoda Mako,Tan Toong Seng,Ngare Isaac,Ueno Takamasa,Saito Akatsuki,Butlertanaka Erika P.,Tanaka Yuri L.,Morizako Nanami,Sawa HirofumiORCID,Ikeda TerumasaORCID,Irie TakashiORCID,Matsuno KeitaORCID,Tanaka ShinyaORCID,Fukuhara TakasukeORCID,Sato Kei,

Abstract

AbstractThe emergence of the Omicron variant of SARS-CoV-2 is an urgent global health concern1. 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 fusion2,3, 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.

Funder

Japan Agency for Medical Research and Development

Publisher

Springer Science and Business Media LLC

Subject

Multidisciplinary

Reference50 articles.

1. WHO. Classification of Omicron (B.1.1.529): SARS-CoV-2 variant of concern; https://www.who.int/news/item/26-11-2021-classification-of-omicron-(b.1.1.529)-sars-cov-2-variant-of-concern (2021).

2. Saito, A. et al. Enhanced fusogenicity and pathogenicity of SARS-CoV-2 Delta P681R mutation. Nature https://doi.org/10.1038/s41586-021-04266-9 (2021).

3. Mlcochova, P. et al. SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion. Nature 599, 114–119 (2021).

4. WHO. Tracking SARS-CoV-2 variants; https://www.who.int/en/activities/tracking-SARS-CoV-2-variants (2021).

5. Liu, Y. et al. The N501Y spike substitution enhances SARS-CoV-2 infection and transmission. Nature https://doi.org/10.1038/s41586-021-04245-0 (2021).

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