Year: 2025
Type: article
Abstract: The SARS-CoV-2 spike protein binds to the angiotensin-converting enzyme 2 (ACE2) receptor to mediate viral entry, with mutations in different variants influencing binding affinity and conformational dynamics. Using large-scale molecular dynamics simulations, we analyzed the Spike-ACE2 complex in the wild-type (WT), Beta, and Delta variants. Our findings reveal significant conformational rearrangements at the interface in Beta and Delta compared to WT, leading to distinct interaction networks and changes in complex stability. Binding free energy analysis further highlights variant-specific differences in ACE2 affinity, with alternative binding modes emerging over the simulation. The results enhance our understanding of spike-ACE2 stoichiometry across variants, providing implications for viral infectivity and therapeutic targeting.
Institutions: Centre National de la Recherche Scientifique, Institut national de recherche en sciences et technologies du numérique, Laboratoire Lorrain de Recherche en Informatique et ses Applications, Université de Lorraine, Institut de Recherche en Infectiologie de Montpellier, Centre de Recherches sur les Macromolécules Végétales, Université Grenoble Alpes
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,230
OpenAlex ID: W4413051326