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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Posted ContentDOI
Allosteric modulation of the SARS-CoV-2 spike conformation
TL;DR: In this article, the effects of ACE2 and antibody binding on the conformational dynamics of S from the Wuhan-1 strain and the B.1 variant were investigated using single-molecule Forster resonance energy transfer (smFRET) imaging.
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Antibody Response to SARS-CoV-2 Membrane Protein in Patients of the Acute and Convalescent Phase of COVID-19.
Philipp Jörrißen,Paula Schütz,Matthias Weiand,Richard Vollenberg,Inga Marie Schrempf,Kevin Ochs,Christopher Frömmel,Phil-Robin Tepasse,Hartmut Schmidt,Andree Zibert +9 more
TL;DR: In this paper, the authors studied the course of the antibody response directed to individual epitopes of SARS-CoV-2 proteins and found that during the acute phase of COVID-19 patients, antibodies are raised to two linear epitopes, located at the very N- and C-termini, showing almost similar levels of reactivity as immunodominant linear epitope derived from the spike and nucleocapsid protein.
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Newcastle Disease Virus-Like Particles Displaying Prefusion-Stabilized SARS-CoV-2 Spikes Elicit Potent Neutralizing Responses
Yongping Yang,Wei Shi,Olubukola M. Abiona,Alexandra Nazzari,Adam S. Olia,Li Ou,Emily Phung,Tyler Stephens,Yaroslav Tsybovsky,Raffaello Verardi,Shuishu Wang,Anne P. Werner,Christina Yap,David R. Ambrozak,Tatsiana Bylund,Tracy Liu,Richard Nguyen,Lingshu Wang,Baoshan Zhang,Tongqing Zhou,Gwo-Yu Chuang,Barney S. Graham,John R. Mascola,Kizzmekia S. Corbett,Peter D. Kwong +24 more
TL;DR: This paper reported the development of Newcastle disease virus-like particles (NDVLPs) displaying the prefusion-stabilized SARS-CoV-2 spike ectodomain (S2P).
Peer ReviewDOI
A Comprehensive Review of Drug Repurposing Strategies against Known Drug Targets of COVID-19
TL;DR: This review attempts to collate both the experimental and computational drug repurposing strategies that have been utilized against significant drug targets of SARS-CoV-2 and the available druggable targets shall also be discussed.
Journal ArticleDOI
Expression and characterization of SARS-CoV-2 spike proteins.
Jeffrey M. Schaub,Chia Wei Chou,Hung-Che Kuo,Kamyab Javanmardi,Ching-Lin Hsieh,Jory A. Goldsmith,Andrea M. DiVenere,Kevin C. Le,Daniel Wrapp,Patrick O. Byrne,Christy K. Hjorth,Nicole V. Johnson,John Ludes-Meyers,Annalee W. Nguyen,Nianshuang Wang,Jason J. Lavinder,Gregory C. Ippolito,Jennifer A. Maynard,Jason S. McLellan,Ilya J. Finkelstein +19 more
TL;DR: In this article, a prefusion-stabilized spike variant, termed HexaPro for six stabilizing proline substitutions, that can be expressed with a yield of >30 mg/L in ExpiCHO cells.
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