Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation.
Daniel Wrapp,Nianshuang Wang,Kizzmekia S. Corbett,Jory A. Goldsmith,Ching-Lin Hsieh,Olubukola M. Abiona,Barney S. Graham,Jason S. McLellan +7 more
TLDR
The authors show that this protein binds at least 10 times more tightly than the corresponding spike protein of severe acute respiratory syndrome (SARS)–CoV to their common host cell receptor, and test several published SARS-CoV RBD-specific monoclonal antibodies found that they do not have appreciable binding to 2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two RBDs.Abstract:
The outbreak of a novel coronavirus (2019-nCoV) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for vaccines, therapeutic antibodies, and diagnostics. To facilitate medical countermeasure development, we determined a 3.5-angstrom-resolution cryo-electron microscopy structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible conformation. We also provide biophysical and structural evidence that the 2019-nCoV S protein binds angiotensin-converting enzyme 2 (ACE2) with higher affinity than does severe acute respiratory syndrome (SARS)-CoV S. Additionally, we tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to 2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two RBDs. The structure of 2019-nCoV S should enable the rapid development and evaluation of medical countermeasures to address the ongoing public health crisis.read more
Citations
More filters
Journal ArticleDOI
Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine.
Fernando P. Polack,Stephen J. Thomas,Nicholas Kitchin,Judith Absalon,Alejandra Gurtman,Stephen Lockhart,John L. Perez,Gonzalo Pérez Marc,Edson D. Moreira,Cristiano Zerbini,Ruth Bailey,Kena A. Swanson,Satrajit Roychoudhury,Kenneth Koury,Ping Li,Warren Kalina,David A. Cooper,Robert W. Frenck,Laura L. Hammitt,Özlem Türeci,Haylene Nell,Axel Schaefer,Serhat Ünal,Dina B. Tresnan,Susan Mather,Philip R. Dormitzer,Ugur Sahin,Kathrin U. Jansen,William C. Gruber +28 more
TL;DR: A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older and safety over a median of 2 months was similar to that of other viral vaccines.
Journal ArticleDOI
Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein.
Alexandra C. Walls,Young-Jun Park,M. Alejandra Tortorici,M. Alejandra Tortorici,Abigail Wall,Andrew T. McGuire,Andrew T. McGuire,David Veesler +7 more
TL;DR: It is demonstrating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination, and it is shown that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of Sars- coV- 2 S and SARS S bind with similar affinities to human ACE2, correlating with the efficient spread of SATS among humans.
Journal ArticleDOI
Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor.
Jun Lan,Jiwan Ge,Jinfang Yu,Sisi Shan,Huan Zhou,Shilong Fan,Qi Zhang,Xuanling Shi,Qisheng Wang,Linqi Zhang,Xinquan Wang +10 more
TL;DR: High-resolution crystal structures of the receptor-binding domain of the spike protein of SARS-CoV-2 and SARS -CoV in complex with ACE2 provide insights into the binding mode of these coronaviruses and highlight essential ACE2-interacting residues.
Journal ArticleDOI
Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2.
TL;DR: Cryo–electron microscopy structures of full-length human ACE2 in the presence of the neutral amino acid transporter B0AT1 with or without the receptor binding domain (RBD) of the surface spike glycoprotein of SARS-CoV-2 are presented, providing important insights into the molecular basis for coronavirus recognition and infection.
Journal ArticleDOI
Multidisciplinary research priorities for the COVID-19 pandemic: a call for action for mental health science.
Emily A. Holmes,Emily A. Holmes,Rory C. O'Connor,V. Hugh Perry,Irene Tracey,Simon Wessely,Louise Arseneault,Clive Ballard,Helen Christensen,Roxane Cohen Silver,Ian P. Everall,Tamsin Ford,Ann John,Thomas Kabir,Kate King,Ira Madan,Susan Michie,Andrew K. Przybylski,Roz Shafran,Angela Sweeney,Carol M. Worthman,Lucy Yardley,Katherine Cowan,Claire Cope,Matthew Hotopf,Edward T. Bullmore +25 more
TL;DR: There is an urgent need for research to address how mental health consequences for vulnerable groups can be mitigated under pandemic conditions, and on the impact of repeated media consumption and health messaging around COVID-19.
References
More filters
Journal ArticleDOI
The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade.
TL;DR: A peculiar furin-like cleavage site is identified in the Spike protein of the 2019-nCoV, lacking in the other SARS-like CoVs, and its potential implication in the development of antivirals is discussed.
Journal ArticleDOI
The Coronavirus Spike Protein Is a Class I Virus Fusion Protein: Structural and Functional Characterization of the Fusion Core Complex
TL;DR: Using biological assays, the HR2 peptide was shown to be a potent inhibitor of virus entry into the cell, as well as of cell-cell fusion.
Journal ArticleDOI
Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody.
Xiaolong Tian,Cheng Li,Ailing Huang,Shuai Xia,Sicong Lu,Zhengli Shi,Lu Lu,Shibo Jiang,Zhenlin Yang,Yanling Wu,Tianlei Ying +10 more
TL;DR: It is reported for the first time that a SARS-CoV-specific human monoclonal antibody,CR3022, could bind potently with 2019-nCoV RBD (KD of 6.3 nM), suggesting that CR3022 may have the potential to be developed as candidate therapeutics, alone or in combination with other neutralizing antibodies, for the prevention and treatment of 2019- nCoV infections.
Journal ArticleDOI
Evidence that TMPRSS2 Activates the Severe Acute Respiratory Syndrome Coronavirus Spike Protein for Membrane Fusion and Reduces Viral Control by the Humoral Immune Response
Ilona Glowacka,Stephanie Bertram,Marcel A. Müller,Paul Allen,Elizabeth J. Soilleux,Susanne Pfefferle,Imke Steffen,Theodros Solomon Tsegaye,Yuxian He,Kerstin Gnirss,Daniela Niemeyer,Heike Schneider,Christian Drosten,Stefan Pöhlmann,Stefan Pöhlmann +14 more
TL;DR: It is shown that TMPRSS2 might promote viral spread and pathogenesis by diminishing viral recognition by neutralizing antibodies and by activating SARS S for cell-cell and virus-cell fusion.
Journal ArticleDOI
Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites.
TL;DR: Data suggest a novel priming mechanism for a viral fusion protein, with a critical proteolytic cleavage event on the SARS-CoV S protein at position 797 (S2′), acting in concert with the S1–S2 cleavage site to mediate membrane fusion and virus infectivity.
Related Papers (5)
A pneumonia outbreak associated with a new coronavirus of probable bat origin
Peng Zhou,Xing-Lou Yang,Xian Guang Wang,Ben Hu,Lei Zhang,Wei Zhang,Hao Rui Si,Yan Zhu,Bei Li,Chao Lin Huang,Hui-Dong Chen,Jing Chen,Yun Luo,Hua Guo,Ren Di Jiang,Meiqin Liu,Ying Chen,Xu Rui Shen,Xi Wang,Xiao Shuang Zheng,Kai Zhao,Quanjiao Chen,Fei Deng,Lin Lin Liu,Bing Yan,Fa Xian Zhan,Yan-Yi Wang,Gengfu Xiao,Zhengli Shi +28 more
Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China
Chaolin Huang,Yeming Wang,Xingwang Li,Lili Ren,Jianping Zhao,Yi Hu,Li Zhang,Guohui Fan,Jiuyang Xu,Xiaoying Gu,Zhenshun Cheng,Ting Yu,Jia'an Xia,Yuan Wei,Wenjuan Wu,Xuelei Xie,Wen Yin,Li Hui,Min Liu,Yan Xiao,Hong Gao,Li Guo,Jungang Xie,Guang-Fa Wang,Rongmeng Jiang,Zhancheng Gao,Qi Jin,Jianwei Wang,Bin Cao +28 more