Mechanical Activation of Spike Fosters SARS-Cov-2 Viral Infection
www.nature.com/cr Cell Research www.cell-research.com ARTICLE OPEN Mechanical activation of spike fosters SARS-CoV-2 viral infection Wei Hu1,15, Yong Zhang2,15, Panyu Fei1,3,15, Tongtong Zhang1,4,15, Danmei Yao1,15, Yufei Gao1,3, Jia Liu5,6, Hui Chen2, Qiao Lu5,6, 5 1 7 8 1 9 10 9 5,6 ✉ Tenny Mudianto✉ , Xinrui Zhang , Chuxuan✉ Xiao , Yang Ye ,✉ Qiming Sun , Jing Zhang , Qi Xie , Pei-Hui Wang , Jun Wang , Zhenhai Li11 , Jizhong Lou 2,12,13 and Wei Chen 1,7,14 © The Author(s) 2021 The outbreak of SARS-CoV-2 (SARS2) has caused a global COVID-19 pandemic. The spike protein of SARS2 (SARS2-S) recognizes host receptors, including ACE2, to initiate viral entry in a complex biomechanical environment. Here, we reveal that tensile force, generated by bending of the host cell membrane, strengthens spike recognition of ACE2 and accelerates the detachment of spike’s S1 subunit from the S2 subunit to rapidly prime the viral fusion machinery. Mechanistically, such mechano-activation is fulfilled by force-induced opening and rotation of spike’s receptor-binding domain to prolong the bond lifetime of spike/ACE2 binding, up to 4 times longer than that of SARS-S binding with ACE2 under 10 pN force application, and subsequently by force-accelerated S1/S2 detachment which is up to ~103 times faster than that in the no-force condition. Interestingly, the SARS2-S D614G mutant, a more infectious variant, shows 3-time stronger force-dependent ACE2 binding and 35-time faster force-induced S1/S2 detachment.
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