On the origins of the Omicron variant of the SARS-CoV-2 virus

TL;DR

This paper proposes that HIV-induced immunocompromise may facilitate SARS-CoV-2 Omicron variant emergence by allowing greater mutational exploration, constrained by biophysical factors like backbone hydrogen bonding, with broader implications for virology.

Contribution

It introduces a first-principles explanation linking HIV coinfection to Omicron's emergence, emphasizing biophysical constraints on viral mutations.

Findings

HIV coinfection may enable SARS-CoV-2 to explore more mutational space.

Mutagenic residues often do not participate in backbone hydrogen bonds.

Viral escape can involve removing backbone hydrogen bonds within physical constraints.

Abstract

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.