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.
【저자키워드】 COVID-19, SARS-CoV-2, coronavirus, neutralization, SARS-CoV-1, spike glycoproteins, ACE2-Fc, CR3022 antibody, human ACE2 receptor, 【초록키워드】 coronavirus disease, ACE2, pandemic, virus, viral entry, glycoprotein, receptor, binding, soluble ACE2, Interaction, deaths, acute respiratory syndrome, human Angiotensin-converting enzyme, positive, trimeric spike, spike trimers, infecting, membrane-bound, anti-SARS-CoV-2 therapeutics, S glycoproteins, responsible, investigated, required, the receptor-binding domain, conformational, exhibit, monomeric, the SARS-CoV-2, 【제목키워드】 ACE2, Human, glycoprotein, SARS-CoV-2 S,