Viral surface geometry shapes influenza and coronavirus spike evolution (preprint)

ABSTRACT

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 is the main target of antibody response. Because of the dense presentation of spikes on the viral surface, not all antigenic sites are targeted equally by antibodies, leading to complex immunodominance patterns. We used 3D coarse-grained computational models to estimate the antibody pressure on the seasonal flu H1N1 and the SARS subgenus spikes. Analyzing publically available sequences, we show that antibody pressure, through the geometrical organization of these 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, at low frequency, several mutations at antibody-accessible positions, which could indicate possible escape as define by our model. 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.