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 Rs3367 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 SARS-CoV-2 showed a different interaction with the ACE2 pocket. Taken together, this study offers molecular insights on RBD-receptor interactions with implications for vaccine design.
【저자키워드】 COVID-19, SARS-CoV-2, spike glycoprotein, angiotensin-converting enzyme 2, SARS Coronavirus, SARS-like bat coronavirus, 【초록키워드】 ACE2, coronavirus, Vaccine design, in silico, Betacoronavirus, Spike protein, RBD, Phylogeny, RaTG13, molecular, Critical, Superimposition, Interaction, Analysis, Contact, similarity, computation, acute respiratory syndrome, complex, residue, domain, cell entry, residues, ACE2-RBD, offer, implication, feature, bind, defined, conserved, reported, composed, addition, the RBD, bat coronavirus, implicated, RBD residue, RBD-receptor, the SARS-CoV-2, 【제목키워드】 coronavirus, identification, domain, feature,