Viral surface geometry shapes influenza and coronavirus spike evolution through antibody pressure.
PLoS Comput Biol
; 17(12): e1009664, 2021 12.
Article
in English
| MEDLINE | ID: covidwho-1571973
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Viral Envelope Proteins
/
Evolution, Molecular
/
Influenza A Virus, H1N1 Subtype
/
Spike Glycoprotein, Coronavirus
/
SARS-CoV-2
Type of study:
Observational study
/
Prognostic study
Limits:
Animals
/
Humans
Language:
English
Journal:
PLoS Comput Biol
Journal subject:
Biology
/
Medical Informatics
Year:
2021
Document Type:
Article
Affiliation country:
Journal.pcbi.1009664
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