Abstract：
The constantly evolving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) fuel the worldwide coronavirus disease (COVID-19) pandemic. The spike protein is essential for the SARS-CoV-2 viral entry and thus has been extensively targeted by therapeutic antibodies. However, mutations along the spike in SARS-CoV-2 VOC and Omicron subvariants have caused more rapid spread and strong antigenic drifts, rendering most of the current antibodies ineffective. Hence, understanding and targeting the molecular mechanism of spike activation is of great interest in curbing the spread and development of new therapeutic approaches. In this review, we summarize the conserved features of spike-mediated viral entry in various SARS-CoV-2 VOC and highlight the converging proteolytic processes involved in priming and activating the spike. We also summarize the roles of innate immune factors in preventing spike-driven membrane fusion and provide outlines for the identification of novel therapeutics against coronavirus infections.
摘要：
不断发展的严重急性呼吸道综合症冠状病毒2（SARS-CoV-2）引起关注的变种（VOC）助长了全球冠状病毒病（COVID-19）大流行。刺突蛋白对于SARS-CoV-2病毒的进入是必不可少的，因此已被治疗性抗体广泛靶向。然而,SARS-CoV-2VOC和Omicron亚变体的突变导致了更快的传播和强烈的抗原漂移，使大多数目前的抗体无效。因此，了解和靶向尖峰激活的分子机制对于遏制新的治疗方法的传播和发展非常感兴趣。在这次审查中,我们总结了在各种SARS-CoV-2VOC中，刺突介导的病毒进入的保守特征，并强调了与引发和激活刺突有关的融合蛋白水解过程。我们还总结了先天免疫因子在预防尖峰驱动膜融合中的作用，并为鉴定针对冠状病毒感染的新疗法提供了概述。
