tetano
Editor, Senior Moderator
Access Microbiol
. 2020 Sep 8;2(11):acmi000166.
doi: 10.1099/acmi.0.000166. eCollection 2020.
Identification of a SARS-like bat coronavirus that shares structural features with the spike glycoprotein receptor-binding domain of SARS-CoV-2
Conchita Fraguas Bringas[SUP] 1 [/SUP], David Booth[SUP] 1 [/SUP]
Affiliations
Abstract
SARS-CoV-2 is a recently emerged coronavirus that binds angiotensin-converting enzyme 2 (ACE2) for cell entry via its receptor-binding domain (RBD) on a surface-expressed spike glycoprotein. Studies show that despite its similarities to severe acute respiratory syndrome (SARS) coronavirus, there are critical differences in key RBD residues when compared to SARS-CoV-2. Here we present a short in silico study, showing that SARS-like bat coronavirus Rs3367 shares a high conservation with SARS-CoV-2 in important RBD residues for ACE2 binding: SARS-CoV-2's Phe486, Thr500, Asn501 and Tyr505; implicated in receptor-binding strength and host-range determination. These features were not shared with other studied bat coronaviruses belonging to the betacoronavirus genus, including RaTG13, the closest reported bat coronavirus to SARS-CoV-2's spike protein. Sequence and phylogeny analyses were followed by the computation of a reliable model of the RBD of SARS-like bat coronavirus Rs3367, which allowed structural insight of the conserved residues. Superimposition of this model on the SARS-CoV-2 ACE2-RBD complex revealed critical ACE2 contacts are also maintained. In addition, residue Asn488[SUB]Rs3367[/SUB] interacted with a previously defined pocket on ACE2 composed of Tyr41, Lys353 and Asp355. When compared to available SARS-CoV-2 crystal structure data, Asn501[SUB]SARS-CoV-2[/SUB] showed a different interaction with the ACE2 pocket. Taken together, this study offers molecular insights on RBD-receptor interactions with implications for vaccine design.
Keywords: COVID-19; SARS coronavirus; SARS-CoV-2; SARS-like bat coronavirus; angiotensin-converting enzyme 2; spike glycoprotein.
. 2020 Sep 8;2(11):acmi000166.
doi: 10.1099/acmi.0.000166. eCollection 2020.
Identification of a SARS-like bat coronavirus that shares structural features with the spike glycoprotein receptor-binding domain of SARS-CoV-2
Conchita Fraguas Bringas[SUP] 1 [/SUP], David Booth[SUP] 1 [/SUP]
Affiliations
- PMID: 33294769
- PMCID: PMC7717483
- DOI: 10.1099/acmi.0.000166
Abstract
SARS-CoV-2 is a recently emerged coronavirus that binds angiotensin-converting enzyme 2 (ACE2) for cell entry via its receptor-binding domain (RBD) on a surface-expressed spike glycoprotein. Studies show that despite its similarities to severe acute respiratory syndrome (SARS) coronavirus, there are critical differences in key RBD residues when compared to SARS-CoV-2. Here we present a short in silico study, showing that SARS-like bat coronavirus Rs3367 shares a high conservation with SARS-CoV-2 in important RBD residues for ACE2 binding: SARS-CoV-2's Phe486, Thr500, Asn501 and Tyr505; implicated in receptor-binding strength and host-range determination. These features were not shared with other studied bat coronaviruses belonging to the betacoronavirus genus, including RaTG13, the closest reported bat coronavirus to SARS-CoV-2's spike protein. Sequence and phylogeny analyses were followed by the computation of a reliable model of the RBD of SARS-like bat coronavirus Rs3367, which allowed structural insight of the conserved residues. Superimposition of this model on the SARS-CoV-2 ACE2-RBD complex revealed critical ACE2 contacts are also maintained. In addition, residue Asn488[SUB]Rs3367[/SUB] interacted with a previously defined pocket on ACE2 composed of Tyr41, Lys353 and Asp355. When compared to available SARS-CoV-2 crystal structure data, Asn501[SUB]SARS-CoV-2[/SUB] showed a different interaction with the ACE2 pocket. Taken together, this study offers molecular insights on RBD-receptor interactions with implications for vaccine design.
Keywords: COVID-19; SARS coronavirus; SARS-CoV-2; SARS-like bat coronavirus; angiotensin-converting enzyme 2; spike glycoprotein.