Unveiling the Complete Spectrum of SARS-CoV-2 Fusion Stages by In Situ Cryo-ET.

ABSTRACT: SARS-CoV-2 entry into host cells is mediated by the spike protein, which drives membrane fusion. While cryo-EM has revealed stable prefusion and postfusion conformations of the spike, the transient intermediate states during the fusion process have remained poorly understood. Here, we designed a near-native viral fusion system that recapitulates SARS-CoV-2 entry and used cryo-electron tomography (cryo-ET) to capture fusion intermediates leading to complete fusion. The spike protein undergoes extensive structural rearrangements, progressing through extended, partially folded, and fully folded intermediates prior to fusion-pore formation, a process that is dependent on protease cleavage and inhibited by the WS6 S2 antibody. Upon interaction with ACE2 receptor dimer, spikes cluster at membran

SUBMITTER: Akıl C 

PROVIDER: S-EPMC11888396 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature