Mahdi Mohamed, Kiarie Irene Wanjiru, Mótyán János András, Hoffka Gyula, Al-Muffti Aya Shamal, Tóth Attila, Tőzsér József
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary.
Department of Infectology, Faculty of Medicine, University of Debrecen, 4031 Debrecen, Hungary.
Viruses. 2025 May 10;17(5):691. doi: 10.3390/v17050691.
Since its emergence in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continuously evolved, giving rise to multiple variants that have significantly altered the trajectory of the COVID-19 pandemic. These variants have resulted in multiple waves of the pandemic, exhibiting characteristic mutations in the spike (S) protein that may have affected receptor interaction, tissue tropism, and cell entry mechanisms. While the virus was shown to primarily utilize the angiotensin-converting enzyme 2 (ACE2) receptor and host proteases such as transmembrane serine protease 2 (TMPRSS2) for entry into host cells, alterations in the S protein have resulted in changes to receptor binding affinity and use of alternative receptors, potentially expanding the virus's ability to infect different cell types or tissues, contributing to shifts in clinical presentation. These changes have been linked to variations in disease severity, the emergence of new clinical manifestations, and altered transmission dynamics. In this paper, we overview the evolving receptor utilization strategies of SARS-CoV-2, focusing on how mutations in the S protein may have influenced viral entry mechanisms and clinical outcomes across the ongoing pandemic waves.
自2019年末出现以来，严重急性呼吸综合征冠状病毒2（SARS-CoV-2）不断进化，产生了多个变种，这些变种显著改变了新冠疫情的发展轨迹。这些变种导致疫情出现多波高峰，其刺突（S）蛋白呈现出特征性突变，这些突变可能影响了受体相互作用、组织嗜性和细胞进入机制。虽然该病毒主要利用血管紧张素转换酶2（ACE2）受体和跨膜丝氨酸蛋白酶2（TMPRSS2）等宿主蛋白酶进入宿主细胞，但S蛋白的改变导致了受体结合亲和力的变化以及替代受体的使用，这可能扩大了病毒感染不同细胞类型或组织的能力，进而导致临床表现的改变。这些变化与疾病严重程度的差异、新临床表现的出现以及传播动态的改变有关。在本文中，我们概述了SARS-CoV-2不断演变的受体利用策略，重点关注S蛋白中的突变如何在持续的疫情浪潮中影响病毒进入机制和临床结果。
