Interaction of Human ACE2 to Membrane-Bound SARS-CoV-1 and SARS-CoV-2 S Glycoproteins
by
Sai Priya Anand 1,2, Yaozong Chen 3, Jérémie Prévost 1,4, Romain Gasser 1,4
, Guillaume Beaudoin-Bussières 1,4, Cameron F. Abrams 5, Marzena Pazgier 3 and Andrés Finzi 1,2,4,*
Sai Priya Anand 1,2, Yaozong Chen 3, Jérémie Prévost 1,4, Romain Gasser 1,4, Guillaume Beaudoin-Bussières 1,4, Cameron F. Abrams 5, Marzena Pazgier 3 and Andrés Finzi 1,2,4,*
1
Centre de Recherche du CHUM, Montréal, QC H2X 0A9, Canada
2
Department of Microbiology and Immunology, McGill University, Montréal, QC H3A 2B4, Canada
3
Infectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814–4712, USA
4
Departement de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC H2X 0A9, Canada
5
Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA 19104, USA
*
Author to whom correspondence should be addressed.
Viruses 2020, 12(10), 1104; https://doi.org/10.3390/v12101104
Received: 3 September 2020 / Revised: 21 September 2020 / Accepted: 24 September 2020 / Published: 29 September 2020
(This article belongs to the Section Antivirals & Vaccines)
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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Keywords:
Coronavirus; SARS-CoV-1; SARS-CoV-2; spike glycoproteins; human ACE2 receptor; ACE2-Fc; CR3022 antibody; neutralization; COVID-19
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
MDPI and ACS Style
Anand, S.P.; Chen, Y.; Prévost, J.; Gasser, R.; Beaudoin-Bussières, G.; Abrams, C.F.; Pazgier, M.; Finzi, A. Interaction of Human ACE2 to Membrane-Bound SARS-CoV-1 and SARS-CoV-2 S Glycoproteins. Viruses 2020, 12, 1104.
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