Fig. 4

Evolutionary events preceding the SARS-CoV-2 emergence and functional impact of amino acids 427N and 436Y. a Phylogenetic representation summarizing the evolutionary events that likely led to the emergence of SARS-CoV-2: hit [1] recombination of the RBD of the Spike protein involving lineages ancestral to SARS-CoV-2, RaTG13, and pangolin sequences (red cross) and SARS-CoV (blue cross); hit [2] SARS-CoV-2 accumulated four nonsynonymous mutations in RBD since its divergence from the MRCA that it shares with RaTG13 and the pangolin CoVs. b Sliding window analysis (length 267 aa) identifies specific regions of SARS-CoV-2 with high divergence from the RaTG13 bat virus in the RBD of Spike (including 427N and 436Y), as well as in the Ubl1, HRV, and SUD domains of nsp3 (non-structural protein 3) within the orf1a polyprotein. c Functional impact of amino acid 427N in the SARS-CoV-2 Spike protein. Interaction between the human ACE2 receptor (green) and the spike protein (pink) based on SARS-CoV-2 (PDB accession code: 6LZG), highlighting the short helix 427-436 that lies at the interface of the Spike-ACE2 interaction. Dashed lines indicate hydrogen bonds between residues. The configuration shown with higher transparency is that of RaTG13 RBD interaction. d Functional impact of amino acid 436Y