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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\u2014from 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.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/mbio.03220-23","type":"journal-article","created":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T13:00:52Z","timestamp":1726491652000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":24,"title":["Molecular and structural insights into SARS-CoV-2 evolution: from BA.2 to XBB subvariants"],"prefix":"10.1128","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-0065-4125","authenticated-orcid":false,"given":"Hisano","family":"Yajima","sequence":"first","affiliation":[{"name":"Laboratory of Medical Virology, Institute for Life and Medical Sciences, Kyoto University, Kyoto, 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