  A possible explanation based on first principles for the appearance of the
Omicron variant of the SARS-CoV-2 virus is proposed involving coinfection with
HIV. The gist is that the resultant HIV-induced immunocompromise allows
SARS-CoV-2 greater latitude to explore its own mutational space. This latitude
is not withoutr estriction, and a specific biophysical constraint is explored.
Specifically, a nearly two- to five-fold discrepancy in backbone hydrogen
bonding is observed between sub-molecules in Protein Data Bank files of the
spike glycoprotein yielding two conclusions: mutagenic residues in the
receptor-binding subunit of the spike much more frequently do not participate
in backbone hydrogen bonds; and a technique of viral escape is therefore to
remove such bonds within physico-chemical and functional constraints. Earlier
work, from which the previous discussion is entirely independent, explains
these phenomena from general principles of free energy, namely, the
metastability of the glycoprotein. The conclusions therefore likely hold more
generally as principles in virology.
