Molecular and structural insights into SARS-CoV-2 evolution: from BA.2 to XBB subvariants
Hisano Yajima,
Tomo Nomai,
Kaho Okumura,
Katsumi Maenaka,
Jumpei Ito,
Takao Hashiguchi,
Kei Sato
Affiliations
Hisano Yajima
Laboratory of Medical Virology, Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan
Tomo Nomai
Laboratory of Biomolecular Science and Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan
Kaho Okumura
Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Katsumi Maenaka
Laboratory of Biomolecular Science and Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan
Jumpei Ito
Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
Takao Hashiguchi
Laboratory of Medical Virology, Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan
Kei Sato
Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
ABSTRACT Due to the incessant emergence of various SARS-CoV-2 variants with enhanced fitness in the human population, controlling the COVID-19 pandemic has been challenging. Understanding how the virus enhances its fitness during a pandemic could offer valuable insights for more effective control of viral epidemics. In this manuscript, we review the evolution of SARS-CoV-2 from early 2022 to the end of 2023—from Omicron BA.2 to XBB descendants. Focusing on viral evolution during this period, we provide concrete examples that SARS-CoV-2 has increased its fitness by enhancing several functions of the spike (S) protein, including its binding affinity to the ACE2 receptor and its ability to evade humoral immunity. Furthermore, we explore how specific mutations modify these functions of the S protein through structural alterations. This review provides evolutionary, molecular, and structural insights into how SARS-CoV-2 has increased its fitness and repeatedly caused epidemic surges during the pandemic.
