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Interaction of Human ACE2 to Membrane-Bound SARS-CoV-1 and SARS-CoV-2 S Glycoproteins
Journal article   Open access   Peer reviewed

Interaction of Human ACE2 to Membrane-Bound SARS-CoV-1 and SARS-CoV-2 S Glycoproteins

Sai Priya Anand, Yaozong Chen, Jérémie Prévost, Romain Gasser, Guillaume Beaudoin-Bussières, Cameron F Abrams, Marzena Pazgier and Andrés Finzi
Viruses, v 12(10), p1104
29 Sep 2020
PMID: 33003587
url
https://doi.org/10.3390/v12101104View
Published, Version of Record (VoR)CC BY V4.0 Open

Abstract

Angiotensin-Converting Enzyme 2 Betacoronavirus - metabolism Betacoronavirus - physiology Carrier Proteins Coronavirus Infections - metabolism Coronavirus Infections - virology COVID-19 Cryoelectron Microscopy HEK293 Cells Humans Pandemics Peptidyl-Dipeptidase A - metabolism Pneumonia, Viral - metabolism Pneumonia, Viral - virology Protein Binding Protein Interaction Domains and Motifs SARS Virus - metabolism SARS Virus - physiology SARS-CoV-2 Severe Acute Respiratory Syndrome - metabolism Severe Acute Respiratory Syndrome - virology Spike Glycoprotein, Coronavirus - metabolism Virus Internalization
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.

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Web of Science research areas
Virology
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