Capture of fusion-intermediate conformations of SARS-CoV-2 spike requires receptor binding and cleavage at either the S1/S2 or S2' site.

ABSTRACT: Although structures of pre- and post-fusion conformations of SARS-CoV-2 spikes have been solved by cryo-electron microscopy, the transient spike conformations that mediate virus fusion with host cell membranes remain poorly understood. In this study, we used a peptide fusion inhibitor corresponding to the heptad repeat 2 (HR2) in the S2 transmembrane subunit of the spike to investigate fusion-intermediate conformations that involve exposure of the highly conserved heptad repeat 1 (HR1). The HR2 peptide disrupts the assembly of the HR1 and HR2 regions of the spike, which form a six-helix bundle during the transition to the post-fusion conformation. We show that binding of the spike S1 subunit to ACE2 is sufficient to induce conformational changes that allow S1 shedding and enable the HR2 pe

SUBMITTER: Lusvarghi S 

PROVIDER: S-EPMC12011290 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature