Interaction of Human ACE2 to Membrane-Bound SARS-CoV-1 and SARS-CoV-2 S Glycoproteins
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 do...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-09-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/12/10/1104 |
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| author | Sai Priya Anand Yaozong Chen Jérémie Prévost Romain Gasser Guillaume Beaudoin-Bussières Cameron F. Abrams Marzena Pazgier Andrés Finzi |
| author_facet | Sai Priya Anand Yaozong Chen Jérémie Prévost Romain Gasser Guillaume Beaudoin-Bussières Cameron F. Abrams Marzena Pazgier Andrés Finzi |
| author_sort | Sai Priya Anand |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T15:57:24Z |
| format | Article |
| id | doaj.art-f80a5aa159eb4c208968ce4068b9d393 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T15:57:24Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-f80a5aa159eb4c208968ce4068b9d3932023-11-20T15:33:44ZengMDPI AGViruses1999-49152020-09-011210110410.3390/v12101104Interaction of Human ACE2 to Membrane-Bound SARS-CoV-1 and SARS-CoV-2 S GlycoproteinsSai Priya Anand0Yaozong Chen1Jérémie Prévost2Romain Gasser3Guillaume Beaudoin-Bussières4Cameron F. Abrams5Marzena Pazgier6Andrés Finzi7Centre de Recherche du CHUM, Montréal, QC H2X 0A9, CanadaInfectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814–4712, USACentre de Recherche du CHUM, Montréal, QC H2X 0A9, CanadaCentre de Recherche du CHUM, Montréal, QC H2X 0A9, CanadaCentre de Recherche du CHUM, Montréal, QC H2X 0A9, CanadaDepartment of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA 19104, USAInfectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814–4712, USACentre de Recherche du CHUM, Montréal, QC H2X 0A9, CanadaSevere 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.https://www.mdpi.com/1999-4915/12/10/1104CoronavirusSARS-CoV-1SARS-CoV-2spike glycoproteinshuman ACE2 receptorACE2-Fc |
| spellingShingle | Sai Priya Anand Yaozong Chen Jérémie Prévost Romain Gasser Guillaume Beaudoin-Bussières Cameron F. Abrams Marzena Pazgier Andrés Finzi Interaction of Human ACE2 to Membrane-Bound SARS-CoV-1 and SARS-CoV-2 S Glycoproteins Viruses Coronavirus SARS-CoV-1 SARS-CoV-2 spike glycoproteins human ACE2 receptor ACE2-Fc |
| title | Interaction of Human ACE2 to Membrane-Bound SARS-CoV-1 and SARS-CoV-2 S Glycoproteins |
| title_full | Interaction of Human ACE2 to Membrane-Bound SARS-CoV-1 and SARS-CoV-2 S Glycoproteins |
| title_fullStr | Interaction of Human ACE2 to Membrane-Bound SARS-CoV-1 and SARS-CoV-2 S Glycoproteins |
| title_full_unstemmed | Interaction of Human ACE2 to Membrane-Bound SARS-CoV-1 and SARS-CoV-2 S Glycoproteins |
| title_short | Interaction of Human ACE2 to Membrane-Bound SARS-CoV-1 and SARS-CoV-2 S Glycoproteins |
| title_sort | interaction of human ace2 to membrane bound sars cov 1 and sars cov 2 s glycoproteins |
| topic | Coronavirus SARS-CoV-1 SARS-CoV-2 spike glycoproteins human ACE2 receptor ACE2-Fc |
| url | https://www.mdpi.com/1999-4915/12/10/1104 |
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