Available online 1 May 2020 In Press, Corrected ProofWhat are Corrected Proof articles? Short Article A Multibasic Cleavage Site in the Spike Protein of SARS-CoV-2 Is Essential for Infection of Human Lung Cells Author links open overlay panelMarkusHoffmann1HannahKleine-Weber12StefanPöhlmann123 https://doi.org/10.1016/j.molcel.2020.04.022Get rights and content open access Highlights • The spike protein of SARS-CoV-2 harbors a multibasic S1/S2 site • The host cell protease furin cleaves the SARS-CoV-2 spike protein at the S1/S2 site • Cleavage at the S1/S2 site is essential for spike-driven viral entry into lung cells Summary The pandemic coronavirus SARS-CoV-2 threatens public health worldwide. The viral spike protein mediates SARS-CoV-2 entry into host cells and harbors a S1/S2 cleavage site containing multiple arginine residues (multibasic) not found in closely related animal coronaviruses. However, the role of this multibasic cleavage site in SARS-CoV-2 infection is unknown. Here, we report that the cellular protease furin cleaves the spike protein at the S1/S2 site and that cleavage is essential for S-protein-mediated cell-cell fusion and entry into human lung cells. Moreover, optimizing the S1/S2 site increased cell-cell, but not virus-cell, fusion, suggesting that the corresponding viral variants might exhibit increased cell-cell spread and potentially altered virulence. Our results suggest that acquisition of a S1/S2 multibasic cleavage site was essential for SARS-CoV-2 infection of humans and identify furin as a potential target for therapeutic intervention. Graphical Abstract
