SARS-CoV-2 spike mutations alter structure and energetics to modulate ACE2 binding immune evasion and viral adaptation.

ABSTRACT: The persistent evolution of SARS-CoV-2 is driven by mutations in the spike protein that modulate receptor binding, immune evasion, and structural stability. In this study, we deciphered the complex host-virus protein-protein interactions using an integrated molecular dynamics (MD) approach to assess the biophysical impacts of key spike mutations, including T478K, T478A, T478E, E484K, G496S, F490S, Q493E, and Y369C. Our findings reveal that viral adaptation hinges on trade-offs between transmissibility and immune escape. For instance, T478K enhances ACE2 binding through structural rigidification and salt bridge formation (e.g., K478-D30), favoring Omicron's increased transmissibility. In contrast, T478A introduces polarity loss and interface relaxation, while T478E leads to electrostatic re

SUBMITTER: Ataya F 

PROVIDER: S-EPMC12569058 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature