@article{a84f23fa960d42c0b8701ac8f2f7c521,
title = "Interaction of human ACE2 to membrane-bound SARS-CoV-1 and SARS-CoV-2 S glycoproteins",
abstract = "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.",
keywords = "ACE2-Fc, COVID-19, CR3022 antibody, Coronavirus, Human ACE2 receptor, Neutralization, SARS-CoV-1, SARS-CoV-2, Spike glycoproteins",
author = "Anand, {Sai Priya} and Yaozong Chen and J{\'e}r{\'e}mie Pr{\'e}vost and Romain Gasser and Guillaume Beaudoin-Bussi{\`e}res and Abrams, {Cameron F.} and Marzena Pazgier and Andr{\'e}s Finzi",
note = "Funding Information: Funding: This work was supported by “Minist{\`e}re de l{\textquoteright}{\'E}conomie et de l{\textquoteright}Innovation du Qu{\'e}bec, Programme de soutien aux organismes de recherche et d{\textquoteright}innovation”, by the Fondation du CHUM, by the Canada{\textquoteright}s COVID-19 Funding: This work was supported by “Minist{\`e}re de l{\textquoteright}{\'E}conomie et de l{\textquoteright}Innovation du Qu{\'e}bec, Programme de Immunity Task Force (CITF), in collaboration with the Canadian Institutes of Health Research (CIHR) and a CIHR soutien aux organismes de recherche et d{\textquoteright}innovation”, by the Fondation du CHUM, by the Canada{\textquoteright}s COVID-19 IAmIm11u6n27it4y toTaMskP FaonrdceR 0(C1IATIF1)2, 9in76 c9otlolaMbo.Pra. tainodn Aw.iFt.hT thhee fCunandaedrsiahnadInnsotitruotleesinofstHudeayltdhe sRigesne,adractha (cCoIllHecRt)ioannadn ad CanIHalRy sfiosu, dnedcaitsiioonn gtorapnut b#l3i5sh24, 1o7r tpor eAp.aFr. aTtihoins wofotrhke wmaasn aulssocrsiuppt.pTohreteadu bthyo trhsed Necaltaiorenanlo Incostmitpueteti onfg Hinetaelrtehs gtsr.aAnt.sF . R01 AI116274 to MP and R01 AI129769 to M.P. and A.F. The funders had no role in study design, data collection are supported by CIHR fellowships. R.G. is supported by a MITACS Acc{\'e}l{\'e}ration postdoctoral fellowship. and analysis, decision to publish, or preparation of the manuscript. The authors declare no competing interests. AA.cFk. niso wthlee dregcmipeinentst: oTfh ae Cauatnhaodras tRheasnekarMch. GCohradiro nonJo Ryceetr(oUv.iSra. lM EHnRtrPy) #fRorCtHheS0m23o5n o9c5l0o–n2a3l2a4n2t4ib. oSd.Py.AC.R, J3.0P2.,2 .and G.B.B. are supported by CIHR fellowships. R.G. is supported by a MITACS Acc{\'e}l{\'e}ration postdoctoral fellowship. Funding Information: This work was supported by ?Minist?re de l'?conomie et de l'Innovation du Qu?bec, Programme de soutien aux organismes de recherche et d'innovation?, by the Fondation du CHUM, by the Canada's COVID-19 Immunity Task Force (CITF), in collaboration with the Canadian Institutes of Health Research (CIHR) and a CIHR foundation grant #352417 to A.F. This work was also supported by the National Institute of Health grants R01 AI116274 to MP and R01 AI129769 to M.P. and A.F. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors declare no competing interests. A.F. is the recipient of a Canada Research Chair on Retroviral Entry #RCHS0235 950-232424. S.P.A., J.P., and G.B.B. are supported by CIHR fellowships. R.G. is supported by a MITACS Acc?l?ration postdoctoral fellowship. Publisher Copyright: {\textcopyright} 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).",
year = "2020",
month = oct,
doi = "10.3390/v12101104",
language = "English",
volume = "12",
journal = "Viruses",
issn = "1999-4915",
number = "10",
}