Conserved High Free Energy Sites in Human Coronavirus Spike Glycoprotein Backbones

Methods previously developed by the author are applied to uncover several sites of interest in the spike glycoproteins of all known human coronaviruses (hCoVs), including SARS-CoV-2 that causes COVID-19. The sites comprise three-dimensional neighborhoods of peptides characterized by four key properties: (1) they pinpoint regions of high free energy in the backbone whose obstruction might interrupt function; (2) by their very definition, they occur rarely in the universe of all gene-encoded proteins that could obviate host response to compounds designed for their interference; (3) they are common to all known hCoV spikes, possibly retaining activity in light of inevitable viral mutation; and (4) they are exposed in the molecular surface of the glycoprotein. These peptides in SARS-CoV-2 are given by the triples of residues (131, 117, 134), (203, 227, 228), and (1058, 730, 731) in its spike.