Distinct conformational states of SARS-CoV-2 spike protein
Yongfei Cai,Yongfei Cai,Jun Zhang,Jun Zhang,Tianshu Xiao,Tianshu Xiao,Hanqin Peng,Sarah M. Sterling,Richard M. Walsh,Shaun Rawson,Sophia Rits-Volloch,Bing Chen,Bing Chen +12 more
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TLDR
Two cryo–electron microscopy structures derived from a preparation of the full-length S protein, representing its prefusion and postfusion conformations, are reported, advancing the understanding of SARS-CoV-2 entry and may guide the development of vaccines and therapeutics.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.read more
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TL;DR: Evidence is presented that Alpha, Beta, and Omicron VOCs were less stable than the ancestral Wuhan-like strain in human biological fluids, which highlights the potential risk of contaminated human Biological fluids in SARS-CoV-2 transmission and contribute to the development of countermeasures against Sars-Cov-2.
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A broad-spectrum macrocyclic peptide inhibitor of the SARS-CoV-2 spike protein
V. Thijssen,Daniel L. Hurdiss,Oliver J. Debski-Antoniak,Matthew Spence,Charlotte Kristel M Franck,A. Norman,Anupriya Aggarwal,Nadia J. Mokiem,David A. A. van Dongen,Stein W. Vermeir,Minglong Liu,Marianthi Chatziandreou,Timo Van Donselaar,Wenjuan Du,Ieva Drulyte,Berend Jan Bosch,Joost Snijder,Stuart Turville,Richard J. Payne,B. Jackson,Frank J. M. van Kuppeveld,Seino A. K. Jongkees +21 more
TL;DR: In this article , the authors used mRNA display under a reprogrammed genetic code to find a spike-targeting macrocyclic peptide that inhibits SARS-CoV-2 Wuhan strain infection by exploiting a new vulnerable site in the spike glycoprotein, which revealed a conserved binding pocket between the receptor binding domain, N-terminal domain and S2 region, distal to the ACE2 receptor interaction site.
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TL;DR: This review will primarily consider mAb that have direct neutralising activity via their targeting of the SARS-CoV-2 Spike (S) protein focussing on the targets of mAb; how they mediate viral neutralisation; their clinical use so far, and their likely place in the therapeutic play book.
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