Abstract
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a major threat to global health. Although varied SARS-CoV-2-related coronaviruses have been isolated from bats and SARS-CoV-2 may infect bat, the structural basis for SARS-CoV-2 to utilize the human receptor counterpart bat angiotensin-converting enzyme 2 (bACE2) for virus infection remains less understood. Here, we report that the SARS-CoV-2 spike protein receptor binding domain (RBD) could bind to bACE2 from Rhinolophus macrotis (bACE2-Rm) with substantially lower affinity compared with that to the human ACE2 (hACE2), and its infectivity to host cells expressing bACE2-Rm was confirmed with pseudotyped SARS-CoV-2 virus and SARS-CoV-2 wild virus. The structure of the SARS-CoV-2 RBD with the bACE2-Rm complex was determined, revealing a binding mode similar to that of hACE2. The analysis of binding details between SARS-CoV-2 RBD and bACE2-Rm revealed that the interacting network involving Y41 and E42 of bACE2-Rm showed substantial differences with that to hACE2. Bats have extensive species diversity and the residues for RBD binding in bACE2 receptor varied substantially among different bat species. Notably, the Y41H mutant, which exists in many bats, attenuates the binding capacity of bACE2-Rm, indicating the central roles of Y41 in the interaction network. These findings would benefit our understanding of the potential infection of SARS-CoV-2 in varied species of bats.
Highlights
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a major threat to global health
We report that the SARS-CoV-2 spike protein receptor binding domain (RBD) could bind to bat angiotensin-converting enzyme 2 (bACE2) from Rhinolophus macrotis with substantially lower affinity compared with that to the human ACE2, and its infectivity to host cells expressing bACE2Rm was confirmed with pseudotyped SARS-CoV-2 virus and SARS-CoV-2 wild virus
The results showed that the SARS-CoV-2 RBD could bind to bACE2-Rm–expressing HEK293T cells with a substantially lower positive rate than that of human ACE2 (hACE2), with 34.5% bACE2-Rm–expressing cells that stained positive versus 91.6% hACE2-expressing cells that stained positive (Fig. 1 A and B). bACE2-Rm contains six potential N-linked glycosylation sites (N53, N90, N329, N546, N660, and N690), and the structure of hACE2 has been revealed to be highly glycosylated [19, 20]
Summary
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a major threat to global health. The analysis of binding details between SARS-CoV-2 RBD and bACE2-Rm revealed that the interacting network involving Y41 and E42 of bACE2-Rm showed substantial differences with that to hACE2. The Y41H mutant, which exists in many bats, attenuates the binding capacity of bACE2-Rm, indicating the central roles of Y41 in the interaction network These findings would benefit our understanding of the potential infection of SARS-CoV-2 in varied species of bats. Pseudotyped and wild SARS-CoV-2 could infect host cells expressing bACE2-Rm. The complex structure of SARS-CoV-2 RBD and bACE2-Rm revealed a conserved binding mode similar to that of hACE2. Mutational analysis revealed that the Y41 and E42 of bACE2-Rm, which contains variations in many bats, play central roles in the interaction with SARS-CoV-2 RBD These findings provide the molecular basis for a better understanding of potential infection of SARS-CoV-2 in bats.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
