Mapping the Evolutionary Space of SARS-CoV-2 Variants to Anticipate Emergence of Subvariants Resistant to COVID-19 Therapeutics.
PLoS Comput Biol
; 20(6): e1012215, 2024 Jun.
Article
en En
| MEDLINE
| ID: mdl-38857308
ABSTRACT
New sublineages of SARS-CoV-2 variants-of-concern (VOCs) continuously emerge with mutations in the spike glycoprotein. In most cases, the sublineage-defining mutations vary between the VOCs. It is unclear whether these differences reflect lineage-specific likelihoods for mutations at each spike position or the stochastic nature of their appearance. Here we show that SARS-CoV-2 lineages have distinct evolutionary spaces (a probabilistic definition of the sequence states that can be occupied by expanding virus subpopulations). This space can be accurately inferred from the patterns of amino acid variability at the whole-protein level. Robust networks of co-variable sites identify the highest-likelihood mutations in new VOC sublineages and predict remarkably well the emergence of subvariants with resistance mutations to COVID-19 therapeutics. Our studies reveal the contribution of low frequency variant patterns at heterologous sites across the protein to accurate prediction of the changes at each position of interest.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Evolución Molecular
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Farmacorresistencia Viral
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Glicoproteína de la Espiga del Coronavirus
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SARS-CoV-2
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COVID-19
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Mutación
Límite:
Humans
Idioma:
En
Año:
2024
Tipo del documento:
Article