Constrained Evolutionary Funnels Shape Viral Immune Escape.

ABSTRACT: Understanding how viral proteins adapt under immune pressure while preserving structural viability is crucial for anticipating the emergence of antibody-resistant variants. Here, we present a probabilistic framework that predicts the evolutionary trajectories of viral escape, revealing immune evasion is funneled through a remarkably small number of viable paths compared to total mutational space. These escape funnels arise from the combined constraints of protein viability and escape from antibodies, which we model using a generative model trained on structural homologs and deep mutational scanning data. We derive a mean-field approximation of evolutionary path ensembles, enabling us to quantify both the fitness and entropy of escape routes. Applied to the SARS-CoV-2 receptor binding domai

SUBMITTER: Huot M 

PROVIDER: S-EPMC12636330 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature