Emergence of SARS-CoV-2 through Recombination and Strong Purifying Selection

Xiaojun Li; Elena E. Giorgi; Manukumar Honnayakanahalli Marichann; Brian Foley; Chuan Xiao; Xiang-peng Kong; Yue Chen; Bette Korber; Feng Gao

Of the bat SL-CoVs that contributed to the recombinant origin of SARS-CoV, only group A viruses bind to ACE2. Group B bat SL-CoVs do not infect human cells (5, 19) and have two deletions in the RBM (figs. 1E and 2A). The short deletion between residues 445 and 449, and in particular the loss of Y449, which forms three hydrogen bonds with ACE2, will significantly affect the overall structure of the RBM (figs. 2F and 2E). The region encompassing the large deletion between residues 473 and 486 contains the loop structure that accounts for the major differences between the S protein of SARS-CoV and SARS-CoV-2 ( fig. 2C ). This deletion causes the loss of contact site F486 and affects the conserved residue F498's hydrophobic interaction with residue M82 on ACE2 (fig. 2F ). These two deletions will render RBM in those CoVs incapable to bind human ACE2. Therefore, recombination may play a role in enabling cross-species transmission in SARS-CoVs through the acquisition of an S gene type that can efficiently bind to the human ACE2 receptor.