Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading worldwide, causing a global pandemic. Bat-origin RaTG13 is currently the most phylogenetically related virus. Here we obtained the complex structure of the RaTG13 receptor binding domain (RBD) with human ACE2 (hACE2) and evaluated binding of RaTG13 RBD to 24 additional ACE2 orthologs. By substituting residues in the RaTG13 RBD with their counterparts in the SARS-CoV-2 RBD, we found that residue 501, the major position found in variants of concern (VOCs) 501Y.V1/V2/V3, plays a key role in determining the potential host range of RaTG13. We also found that SARS-CoV-2 could induce strong cross-reactive antibodies to RaTG13 and identified a SARS-CoV-2 monoclonal antibody (mAb), CB6, that could cross-neutralize RaTG13 pseudovirus. These results elucidate the receptor binding and host adaption mechanisms of RaTG13 and emphasize the importance of continuous surveillance of coronaviruses (CoVs) carried by animal reservoirs to prevent another spillover of CoVs.
Keywords: ACE2; COVID-19; RBD; RaTG13; SARS-CoV-2; intermediate horseshoe bat.
【저자키워드】 COVID-19, SARS-CoV-2, ACE2, RBD, RaTG13, intermediate horseshoe bat., 【초록키워드】 severe acute respiratory syndrome coronavirus 2, coronavirus, monoclonal antibody, variants of concern, severe acute respiratory syndrome Coronavirus, virus, variants, hACE2, Receptor binding domain, global pandemic, human ACE2, Surveillance, pseudovirus, VOCs, RaTG13, host range, respiratory, mechanism, binding, mAb, cross-neutralize, Receptor binding, animal reservoirs, SARS-CoV-2 RBD, cross-reactive antibody, horseshoe bat, continuous surveillance, acute respiratory syndrome, intermediate horseshoe bat, acute respiratory syndrome coronavirus, ACE2 orthologs, complex, residue, CoVs, residues, reservoir, Host, Prevent, carried, evaluated, induce, phylogenetically, the SARS-CoV-2, 【제목키워드】 Human, virus, RaTG13, molecular basis,