Fig. 5

The ancestral recombination event at RBD involving SARS-CoV/SARS-CoV-2 is associated with increased affinity to hACE2. Boxplots represent the distribution of the binding energies of the RBD of each viral strain to hACE2, as inferred by Rosetta. Viral strains (and the analyzed MRCAs) have been labeled with numbers in a hierarchical order, as follows. Outgroup sequence: 0, MRCA from which the MRCA of the recombination cluster derives: 1, MRCA of the recombination event: 2, MRCA of SARS-CoV and SARS-CoV-2 lineages: 1, MRCA of SARS and its bat-SL-CoV relatives: 4A, SARS-CoV: 4B, MRCA of RaTG13, Pangolin-CoV and SARS-CoV-2: 3A, Pangolin-CoV: 3B-P, RaTG13: 3B-R, SARS-CoV-2: 3B-S. The diagram on the right summarizes the progressive increase in binding affinity along the evolutionary trajectories leading to SARS-CoV and SARS-CoV-2. All strains involved in the SARS/SARS-CoV-2 recombination event, including their MRCA, exhibit higher binding affinity (lower binding energy) than the bat SARS-like CoV used as outgroup (MG772933, “0”). Binding affinity increased further along the evolution of human-infecting Sarbecoviruses (SARS-CoV, SARS-CoV-2). The highest binding affinity among all strains analyzed is found in SARS-CoV-2 (“3B-S”) and its MRCA shared with Pangolin-CoV and RaTG13 (“3A”)