tetano
Editor, Senior Moderator
Viruses
. 2020 Sep 29;12(10):E1104.
doi: 10.3390/v12101104.
Interaction of Human ACE2 to Membrane-Bound SARS-CoV-1 and SARS-CoV-2 S Glycoproteins
Sai Priya Anand[SUP] 1 2 [/SUP], Yaozong Chen[SUP] 3 [/SUP], J?r?mie Pr?vost[SUP] 1 4 [/SUP], Romain Gasser[SUP] 1 4 [/SUP], Guillaume Beaudoin-Bussi?res[SUP] 1 4 [/SUP], Cameron F Abrams[SUP] 5 [/SUP], Marzena Pazgier[SUP] 3 [/SUP], Andr?s Finzi[SUP] 1 2 4 [/SUP]
Affiliations
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; SARS-CoV-1; SARS-CoV-2; human ACE2 receptor; neutralization; spike glycoproteins.
. 2020 Sep 29;12(10):E1104.
doi: 10.3390/v12101104.
Interaction of Human ACE2 to Membrane-Bound SARS-CoV-1 and SARS-CoV-2 S Glycoproteins
Sai Priya Anand[SUP] 1 2 [/SUP], Yaozong Chen[SUP] 3 [/SUP], J?r?mie Pr?vost[SUP] 1 4 [/SUP], Romain Gasser[SUP] 1 4 [/SUP], Guillaume Beaudoin-Bussi?res[SUP] 1 4 [/SUP], Cameron F Abrams[SUP] 5 [/SUP], Marzena Pazgier[SUP] 3 [/SUP], Andr?s Finzi[SUP] 1 2 4 [/SUP]
Affiliations
- PMID: 33003587
- DOI: 10.3390/v12101104
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; SARS-CoV-1; SARS-CoV-2; human ACE2 receptor; neutralization; spike glycoproteins.