9 Structural basis for the evolution of SARS-CoV-2 variants and vaccine-antigen design橋口 隆生1) Sasaki J, Sato A, Sasaki M, et al. X-206 exhibits broad-spectrum anti-β-coronavirus activity, covering SARS-CoV-2 variants and drug-resistant isolates. Antiviral Res. 2024. 232:106039.2) Yajima H, Anraku Y, Kaku Y, et al. Structural basis for receptor-binding domain mobility of the spike in SARS-CoV-2 BA.2.86 and JN.1. Nat Commun. 2024. 15(1):8574.3) Yajima H, Nomai T, Okumura K, et al. Molecular and structural insights into SARS-CoV-2 evolution: from BA.2 to XBB sub. mBio. 2024. 15(10):e0322023.4) Ito J, Suzuki R, Uriu K, et al. Convergent evolution of SARS-CoV-2 Omicron subvariants leading to the emergence of BQ.1.1 variant. Nat Commun. 2023. 14(1):2671.5) Kimura I, Yamasoba D, Tamura T, et al. Virological characteristics of the SARS-CoV-2 Omicron BA.2 subvariants including BA.4 and BA.5. Cell. 2022. 185(21):3992-4007.京都大学 医生物学研究所 ウイルス制御分野4. SARS-CoV-2 変異株の進化の構造基盤と構造情報を活用した抗原デザインSince 2019, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has undergone mutations, resulting in pandemic and epidemic waves. The SARS-CoV-2 spike protein, crucial for cellular entry, binds to the ACE2 receptor exclusively when its receptor-binding domain (RBD) adopts the “up” conformation. This spike protein also mediates the membrane fusion. Taken together, the spike protein plays the most important role for its cellular tropism. On the other hand, the same spike protein is also the sole target of neutralizing antibodies, making it the most important antigen from our immune system. Especially, the RBD is the primary binding target of neutralizing antibodies. Here, we present the evolution of SARS-CoV-2 spike protein from 2022 to 2024—from Omicron BA.2 to JN.1 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 protein, including its binding affinity to the ACE2 receptor and its ability to evade humoral immunity. Furthermore, we explored which variants and structural states function as an antigen that neutralizes a broader range of variants. I would like to discuss the structural basis for the evolution of SARS-CoV-2 variants and vaccine-antigen design.laboratory of Medical Virology, Institute for Life and Medical Sciences, Kyoto University Takao Hashiguchi
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