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

The evolution of circulating viruses is shaped by their need to evade antibody response, which mainly targets the glycoprotein (spike). However, not all antigenic sites are targeted equally by antibodies, leading to complex immunodominance patterns. We used 3D computational models to estimate antibody pressure on the seasonal influenza H1N1 and SARS spikes. Analyzing publically available sequences, we show that antibody pressure, through the geometrical organization of spikes on the viral surface, shaped their mutability. Studying the mutability patterns of SARS-CoV-2 and the 2009 H1N1 pandemic spikes, we find that they are not predominantly shaped by antibody pressure. However, for SARS-CoV-2, we find that over time, it acquired mutations at antibody-accessible positions, which could indicate possible escape as define by our model. We offer a geometry-based approach to predict and rank the probability of surface resides of SARS-CoV-2 spike to acquire antibody escaping mutations.