The SARS-CoV-2 spike S375F mutation characterizes the Omicron BA.1 variant
Izumi Kimura, Daichi Yamasoba, Hesham Nasser, Jiří Zahradník, Yusuke Kosugi, Jiaqi Wu, Kayoko Nagata, Keiya Uriu, Yuri Tanaka, Jumpei Ito, Ryo Shimizu, Toong Seng Tan, Erika P. Butlertanaka, Hiroyuki Asakura, Kenji Sadamasu, Kazuhisa Yoshimura, Takamasa Ueno, Akifumi Takaori‐Kondo, Gideon Schreiber, Mako Toyoda, Kotaro Shirakawa, Takashi Irie, Akatsuki Saito, So Nakagawa, Terumasa Ikeda, Kei Sato
Abstract
Recent studies have revealed the unique virological characteristics of Omicron, particularly those of its spike protein, such as less cleavage efficacy in cells, reduced ACE2 binding affinity, and poor fusogenicity. However, it remains unclear which mutation(s) determine these three virological characteristics of Omicron spike. Here, we show that these characteristics of the Omicron spike protein are determined by its receptor-binding domain. Of interest, molecular phylogenetic analysis revealed that acquisition of the spike S375F mutation was closely associated with the explosive spread of Omicron in the human population. We further elucidated that the F375 residue forms an interprotomer pi-pi interaction with the H505 residue of another protomer in the spike trimer, conferring the attenuated cleavage efficiency and fusogenicity of Omicron spike. Our data shed light on the evolutionary events underlying the emergence of Omicron at the molecular level.