Detailed phylogenetic analysis of SARS-CoV-2 reveals latent capacity to bind human ACE2 receptor

SARS-CoV-2 is a once-in-a-century pandemic, having emerged suddenly as a highly infectious viral pathogen. Previous phylogenetic analyses show its closest known evolutionary relative to be a virus isolated from bats (RaTG13), with a common assumption that SARS-CoV-2 evolved from a zoonotic ancestor via recent genetic changes (likely in the Spike protein receptor binding domain, or RBD) that enabled it to infect humans. We used detailed phylogenetic analysis, ancestral sequence reconstruction, and molecular dynamics simulations to examine the Spike-RBD functional evolution, finding to our surprise that it has likely possessed high affinity for human cell targets since at least 2013.