Cleaved vs. Uncleaved: How Furin Cleavage Reshapes the Conformational Landscape of SARS-CoV-2 Spike.

ABSTRACT: The SARS-CoV-2 Spike protein is the primary target for vaccine design, with immunogens typically engineered to enhance stability by introducing proline mutations (2P) and mutating or deleting the Furin Cleavage Site (FCS). While these modifications improve structural integrity, studies suggest that furin cleavage can play a functional role in Spike protein dynamics, potentially enhancing ACE2 receptor binding. However, the impact of this cleavage on the unbound form of the Spike protein remains unclear. In this study, we use extensive all-atom molecular dynamics (MD) simulations to compare the structural and dynamic properties of cleaved and uncleaved Spike proteins in their pre-fusion, unbound state. Our results show that Furin cleavage significantly alters allosteric communication within

SUBMITTER: Mani N 

PROVIDER: S-EPMC11952566 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature