Viral surface geometry shapes the coronavirus and influenza virus spike evolution through antibody pressure

The evolution of circulating viruses is shaped by their need to evade the adaptive immune system. The spike protein which mediates entry to the host cell, presented at a high density on the viral surface, is the main target of antibody response. As a result, antibody pressure acting on the spike forces it to mutate, leading to genetic drift. Using a computational model based on coarse-grained 3d structure and publically available sequences, we show that presentation geometry, through antibody pressure, shaped, to the first order, the surface mutability map of the SARS family and the seasonal flu H1N1 spikes.

Studying the mutability patterns of SARS-CoV-2 and the 2009 H1N1 pandemic spikes, we find that they are not predominantly geometrically shaped by antibody pressure. However, for SARS-CoV-2, we find that over time, it acquired, at low frequency, several mutations at antibody-accessible positions, which could indicate possible antibody escape. Hence, we offer a geometry-based approach to estimate and assess whether a pandemic virus is changing its mutational pattern to that indicative of a circulating virus.