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Viral surface geometry shapes influenza and coronavirus spike evolution through antibody pressure
Name
journal.pcbi.1009664.pdf
Description
Published version
Size
3.09 MB
Format
Adobe PDF
Checksum (MD5)
653a4de30be1dee96bb1bef56498fd84
Author(s)
Amitai, Assaf
Date Issued
December 2021
Journal
PLOS Computational Biology
Publisher
Public Library of Science (PLoS)
Citation
Amitai, Assaf. 2021. "Viral surface geometry shapes influenza and coronavirus spike evolution through antibody pressure." PLOS Computational Biology, 17 (12).
Version
Final published version
Abstract
The evolution of circulating viruses is shaped by their need to evade antibody response, which mainly targets the viral spike. Because of the high density of spikes on the viral surface, not all antigenic sites are targeted equally by antibodies. We offer here a geometry-based approach to predict and rank the probability of surface residues of SARS spike (S protein) and influenza H1N1 spike (hemagglutinin) to acquire antibody-escaping mutations utilizing in-silico models of viral structure. We used coarse-grained MD simulations to estimate the on-rate (targeting) of an antibody model to surface residues of the spike protein. Analyzing publicly available sequences, we found that spike surface sequence diversity of the pre-pandemic seasonal influenza H1N1 and the sarbecovirus subgenus highly correlates with our model prediction of antibody targeting. In particular, we identified an antibody-targeting gradient, which matches a mutability gradient along the main axis of the spike. This identifies the role of viral surface geometry in shaping the evolution of circulating viruses. For the 2009 H1N1 and SARS-CoV-2 pandemics, a mutability gradient along the main axis of the spike was not observed. Our model further allowed us to identify key residues of the SARS-CoV-2 spike at which antibody escape mutations have now occurred. Therefore, it can inform of the likely functional role of observed mutations and predict at which residues antibody-escaping mutation might arise.
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
10.1371/journal.pcbi.1009664
