Centre de Recherche du CHUM, Montréal, QC H2X 0A9, Canada.
Department of Microbiology and Immunology, McGill University, Montréal, QC H3A 2B4, Canada.
Viruses. 2020 Sep 29;12(10):1104. doi: 10.3390/v12101104.
Severe acute respiratory syndrome virus 2 (SARS-CoV-2) is responsible for the current global coronavirus disease 2019 (COVID-19) pandemic, infecting millions of people and causing hundreds of thousands of deaths. The viral entry of SARS-CoV-2 depends on an interaction between the receptor-binding domain of its trimeric spike glycoprotein and the human angiotensin-converting enzyme 2 (ACE2) receptor. A better understanding of the spike/ACE2 interaction is still required to design anti-SARS-CoV-2 therapeutics. Here, we investigated the degree of cooperativity of ACE2 within both the SARS-CoV-2 and the closely related SARS-CoV-1 membrane-bound S glycoproteins. We show that there exist differential inter-protomer conformational transitions between both spike trimers. Interestingly, the SARS-CoV-2 spike exhibits a positive cooperativity for monomeric soluble ACE2 binding when compared to the SARS-CoV-1 spike, which might have more structural restraints. Our findings can be of importance in the development of therapeutics that block the spike/ACE2 interaction.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）是导致当前全球 2019 年冠状病毒病（COVID-19）大流行的罪魁祸首，感染了数百万人，并导致数十万人死亡。SARS-CoV-2 的病毒进入依赖于其三聚体刺突糖蛋白的受体结合结构域与人类血管紧张素转换酶 2（ACE2）受体之间的相互作用。为了设计抗 SARS-CoV-2 的治疗方法，仍需要更好地了解刺突/ACE2 的相互作用。在这里，我们研究了 SARS-CoV-2 和密切相关的 SARS-CoV-1 膜结合 S 糖蛋白中 ACE2 的协同程度。我们表明，两种刺突三聚体之间存在不同的同三聚体构象转变。有趣的是，与 SARS-CoV-1 刺突相比，SARS-CoV-2 刺突在单体可溶性 ACE2 结合时表现出正协同性，这可能具有更多的结构限制。我们的研究结果对于开发阻断刺突/ACE2 相互作用的治疗方法具有重要意义。
