SARS-CoV-2 spike S375F mutation characterizes the Omicron BA.1 variant

• Published in: bioRxiv 2022-04
• Main Authors: Kimura, Izumi, Yamasoba, Daichi, Nasser, Hesham, Zahradnik, Jiri, Kosugi, Yusuke, Wu, Jiaqi, Nagata, Kayoko, Uriu, Keiya, Tanaka, Yuri L, Ito, Jumpei, Shimizu, Ryo, Tan, Toong Seng, Butlertanaka, Erika P, Asakura, Hiroyuki, Sadamasu, Kenji, Yoshimura, Kazuhisa, Ueno, Takamasa, Takaori-Kondo, Akifumi, Schreiber, Gideon, The Genotype To Phenotype Japan (G2p-Japan) Consortium, Toyoda, Mako, Shirakawa, Kotaro, Irie, Takashi, Saito, Akatsuki, Nakagawa, So, Ikeda, Terumasa, Sato, Kei
• Format: Article
• Language: eng ; jpn
• Subjects: Mutation; Phylogeny; Severe acute respiratory syndrome coronavirus 2; Spike protein; Trimers; Vaccines
• DOI: 10.1101/2022.04.03.486864

Recent studies have revealed the unique virological characteristics of Omicron, the newest SARS-CoV-2 variant of concern, such as pronounced resistance to vaccine-induced neutralizing antibodies, less efficient cleavage of the spike protein, and poor fusogenicity. However, it remains unclear which mutation(s) in the spike protein determine the virological characteristics of Omicron. Here, we show that the representative characteristics of the Omicron spike are determined by its receptor-binding domain. Interestingly, the molecular phylogenetic analysis revealed that the acquisition of the spike S375F mutation was closely associated with the explosive spread of Omicron in the human population. We further elucidate that the F375 residue forms an interprotomer pi-pi interaction with the H505 residue in another protomer in the spike trimer, which confers the attenuated spike cleavage efficiency and fusogenicity of Omicron. Our data shed light on the evolutionary events underlying Omicron emergence at the molecular level. Competing Interest Statement The authors have declared no competing interest.