Li Yajuan, Zheng Peiyi, Liu Tingting, Shi Cuixiao, Wang Bo, Xu Yuanhong, Jin Tengchuan
Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Laboratory of Structural Immunology, CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Front Mol Biosci. 2022 Jul 12;9:930931. doi: 10.3389/fmolb.2022.930931. eCollection 2022.
The most recent human coronaviruses including severe acute respiratory syndrome coronavirus-2 causing severe respiratory tract infection and high pathogenicity bring significant global public health concerns. Infections are initiated by recognizing host cell receptors by coronavirus spike protein S1 subunit, and then S2 mediates membrane fusion. However, human coronavirus spikes undergo frequent mutation, which may result in diverse pathogenesis and infectivity. In this review, we summarize some of these recent structural and mutational characteristics of RBD of human coronavirus spike protein and their interaction with specific human cell receptors and analyze the structural requirements and plasticity of RBD. Stability of spike protein, affinity toward receptor, virus fitness, and infectivity are the factors controlling the viral tropisms. Thus, understanding the molecular details of RBDs and their mutations is critical in deciphering virus evolution. Structural information of spike and receptors of human coronaviruses not only reveals the molecular mechanism of host-microbe interaction and pathogenesis but also helps develop effective drug to control these infectious pathogens and cope with the future emerging coronavirus outbreaks.
包括导致严重呼吸道感染和高致病性的严重急性呼吸综合征冠状病毒2在内的最新人类冠状病毒引起了全球重大公共卫生关注。冠状病毒刺突蛋白S1亚基识别宿主细胞受体引发感染，随后S2介导膜融合。然而，人类冠状病毒刺突蛋白经常发生突变，这可能导致不同的发病机制和传染性。在本综述中，我们总结了人类冠状病毒刺突蛋白RBD的一些最新结构和突变特征及其与特定人类细胞受体的相互作用，并分析了RBD的结构要求和可塑性。刺突蛋白的稳定性、对受体的亲和力、病毒适应性和传染性是控制病毒嗜性的因素。因此，了解RBD及其突变的分子细节对于破译病毒进化至关重要。人类冠状病毒刺突蛋白和受体的结构信息不仅揭示了宿主-微生物相互作用和发病机制的分子机制，还有助于开发有效的药物来控制这些传染性病原体，并应对未来新出现的冠状病毒疫情。
