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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Furin cleavage of the SARS-CoV-2 spike is modulated by O -glycosylation.
Liping Zhang,Matthew Mann,Zulfeqhar Syed,Hayley M Reynolds,E Tian,Nadine L. Samara,Darryl C. Zeldin,Lawrence A. Tabak,Kelly G. Ten Hagen +8 more
TL;DR: In this paper, the SARS-CoV-2 coronavirus responsible for the global pandemic contains a novel furin cleavage site in the spike protein (S) that increases viral infectivity and syncytia formation in cells.
Posted ContentDOI
S-Trimer, a COVID-19 subunit vaccine candidate, induces protective immunity in nonhuman primates
Joshua G. Liang,Danmei Su,Tian-Zhang Song,Yilan Zeng,Weijin Huang,Jinhua Wu,Rong Xu,Peiwen Luo,Xiaofang Yang,Xiaodong Zhang,Shuangru Luo,Ying Liang,Xinglin Li,Jiaju Huang,Qiang Wang,Xueqin Huang,Qingsong Xu,Mei Luo,Anliang Huang,Dongxia Luo,Chenyan Zhao,Fan Yang,Jian-Bao Han,Yong-Tang Zheng,Peng Liang +24 more
TL;DR: S-Trimer, a native-like trimeric subunit vaccine candidate for COVID-19 based on Trimer-Tag technology, is described, which may be an important new platform technology for scalable production and rapid development of safe and effective subunit vaccines against current and future emerging RNA viruses.
Journal ArticleDOI
Broadly neutralizing antibodies target the coronavirus fusion peptide
Cherrelle Dacon,C Tucker,Linghang Peng,Chang-Chun D Lee,Ting-Hui Lin,Meng Yuan,Yu Cong,Lingshu Wang,Lauren Purser,Jazmean K. Williams,Chul Woo Pyo,Ivan Kosik,Zhe Hu,Divya Mohan,Andrew J R Cooper,Mary E. Peterson,Jeff Skinner,Saurabh Dixit,Erin Kollins,Louis Huzella,Donna L. Perry,Russell Byrum,Sanae Lembirik,D. W. Drawbaugh,Brett P. Eaton,Yi Zhang,Eun Sung Yang,Man Chen,Kwanyee Leung,Rona Singer Weinberg,Amarendra Pegu,Daniel E. Geraghty,Edgar Davidson,Iyadh Douagi,Susan Moir,Jonathan W. Yewdell,Connie S. Schmaljohn,Peter D. Crompton,Michael R. Holbrook,David Nemazee,John R. Mascola,Ian A. Wilson,Joshua Hoong Yu Tan +42 more
TL;DR: This work uses an epitope-agnostic approach to identify six monoclonal antibodies that bind to spike proteins from all seven human-infecting coronaviruses, and highlights the fusion peptide as a candidate epitope for next-generation coronavirus vaccine development.
Journal ArticleDOI
COVID-19 Vaccines: Current Understanding on Immunogenicity, Safety, and Further Considerations.
TL;DR: In this article, the efficacy, immunogenicity and safety data from clinical reports on different COVID-19 vaccines have been analyzed, and the key remaining challenges, possible strategies for addressing them and the expected improvements in the next generation of COVID19 vaccines.
Posted ContentDOI
SARS-CoV-2 variant B.1.617 is resistant to Bamlanivimab and evades antibodies induced by infection and vaccination
Markus Hoffmann,Markus Hoffmann,Heike Hofmann-Winkler,Nadine Krueger,Amy Kempf,Amy Kempf,Inga Nehlmeier,Luise Graichen,Luise Graichen,Anzhalika Sidarovich,Anzhalika Sidarovich,Anna-Sophie Moldenhauer,Martin Sebastian Winkler,Sebastian R. Schulz,Hans-Martin Jaeck,Metodi V. Stankov,Georg M. N. Behrens,Stefan Poehlmann,Stefan Poehlmann +18 more
TL;DR: In this article, the authors analyzed whether B.1.617 is more adept in entering cells and/or evades antibody responses, and revealed that antibody evasion may contribute to the rapid spread of this variant.
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