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
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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
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Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen
Jesper Pallesen,Nianshuang Wang,Kizzmekia S. Corbett,Daniel Wrapp,Robert N. Kirchdoerfer,Hannah L. Turner,Christopher A. Cottrell,Michelle M. Becker,Lingshu Wang,Wei Shi,Wing-Pui Kong,Erica L. Andres,Arminja N. Kettenbach,Mark R. Denison,Mark R. Denison,James D. Chappell,Barney S. Graham,Andrew B. Ward,Jason S. McLellan +18 more
TL;DR: An engineering strategy for stabilization of soluble S proteins in the prefusion conformation is described, which results in greatly increased expression, conformational homogeneity, and elicitation of potent antibody responses, and an engineered immunogen is able to elicit high neutralizing antibody titers against MERS-CoV.
Journal ArticleDOI
ISOLDE: a physically realistic environment for model building into low-resolution electron-density maps
TL;DR: ISOLDE is an interactive molecular-dynamics environment for rebuilding models against experimental cryo-EM or crystallographic maps and reinforces the need for great care when validating models built into low-resolution data.
Journal ArticleDOI
Collaboration gets the most out of software
Andrew Morin,Ben Eisenbraun,Jason Key,Paul C. Sanschagrin,Michael A Timony,Michelle Ottaviano,Piotr Sliz +6 more
TL;DR: By centralizing many of the tasks associated with the upkeep of scientific software, SBGrid allows researchers to spend more of their time on research.
Journal ArticleDOI
cisTEM, user-friendly software for single-particle image processing
TL;DR: New open-source software called cisTEM (computational imaging system for transmission electron microscopy) for the processing of data for high-resolution electron cryo-microscopy and single-particle averaging is developed, optimized to enable processing of typical datasets on a high-end, CPU-based workstation in half a day or less, comparable to GPU-accelerated processing.
Journal ArticleDOI
Cryo-EM structure of the SARS coronavirus spike glycoprotein in complex with its host cell receptor ACE2
TL;DR: Structural comparisons suggested that the SARS-CoV S glycoprotein retains a prefusion architecture after trypsin cleavage into the S1 and S2 subunits and acidic pH treatment, however, binding to the receptor opens up the receptor-binding domain of S1, which could promote the release of the S 1-ACE2 complex and S1 monomers from the prefusion spike and trigger the pre- to postfusion conformational transition.
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