Distinct conformational states of SARS-CoV-2 spike protein.

Cai, Yongfei; Zhang, Jun; Xiao, Tianshu; Peng, Hanqin; Sterling, Sarah M; Walsh, Richard M; Rawson, Shaun; Rits-Volloch, Sophia et al. · Science · 2020

basic_science · Level V

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Abstract

Intervention strategies are urgently needed to control the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The trimeric viral spike (S) protein catalyzes fusion between viral and target cell membranes to initiate infection. Here, we report two cryo-electron microscopy structures derived from a preparation of the full-length S protein, representing its prefusion (2.9-angstrom resolution) and postfusion (3.0-angstrom resolution) conformations, respectively. The spontaneous transition to the postfusion state is independent of target cells. The prefusion trimer has three receptor-binding domains clamped down by a segment adjacent to the fusion peptide. The postfusion structure is strategically decorated by N-linked glycans, suggesting possible protective roles against host immune responses and harsh external conditions. These findings advance our understanding of SARS-CoV-2 entry and may guide the development of vaccines and therapeutics.

Medical subject headings