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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Structural Basis for Potent Neutralization of Betacoronaviruses by Single-Domain Camelid Antibodies.
Daniel Wrapp,Dorien De Vlieger,Kizzmekia S. Corbett,Gretel M. Torres,Nianshuang Wang,Wander Van Breedam,Kenny Roose,Loes van Schie,Markus Hoffmann,Stefan Pöhlmann,Barney S. Graham,Nico Callewaert,Bert Schepens,Xavier Saelens,Jason S. McLellan +14 more
TL;DR: The isolation of single-domain antibodies (VHHs) from a llama immunized with prefusion-stabilized coronavirus spikes provide a molecular basis for the neutralization of pathogenic betacoronaviruses by VHHs and suggest that these molecules may serve as useful therapeutics during coronav virus outbreaks.
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SARS-CoV-2 and Coronavirus Disease 2019: What We Know So Far.
TL;DR: The scientific community raced to uncover the origin of the virus, understand the pathogenesis of the disease, develop treatment options, define the risk factors, and work on vaccine development.
Posted ContentDOI
The D614G mutation in the SARS-CoV-2 spike protein reduces S1 shedding and increases infectivity
Lizhou Zhang,Cody B. Jackson,Huihui Mou,Amrita Ojha,Erumbi S. Rangarajan,Tina Izard,Michael Farzan,Hyeryunc Choe +7 more
TL;DR: Results show SG614 is more stable than SD614, consistent with epidemiological data suggesting that viruses with SG614 transmit more efficiently, and the pseudoviruses containing these S proteins were neutralized with comparable efficiencies by convalescent plasma.
Journal ArticleDOI
Virology, transmission, and pathogenesis of SARS-CoV-2.
TL;DR: A broad update on the emerging understanding of SARS-CoV-2 pathophysiology, including virology, transmission dynamics, and the immune response to the virus is provided.
Journal ArticleDOI
Broad neutralization of SARS-related viruses by human monoclonal antibodies.
Anna Z. Wec,Daniel Wrapp,Andrew S. Herbert,Daniel P. Maurer,Denise Haslwanter,Mrunal Sakharkar,Rohit K. Jangra,M. Eugenia Dieterle,Asparouh Lilov,Deli Huang,Longping V. Tse,Nicole V. Johnson,Ching-Lin Hsieh,Nianshuang Wang,Juergen Hermann Nett,Elizabeth Champney,Irina Burnina,Michael G. Brown,Shu Lin,Melanie Sinclair,Carl Hirschie Johnson,Sarat Pudi,Robert H. Bortz,Ariel S. Wirchnianski,Ethan Laudermilch,Catalina Florez,J. Maximilian Fels,Cecilia M. O’Brien,Barney S. Graham,David Nemazee,Dennis R. Burton,Ralph S. Baric,James E. Voss,Kartik Chandran,John M. Dye,Jason S. McLellan,Laura M. Walker +36 more
TL;DR: Hundreds of antibodies against the viral spike protein of SARS-CoV-2 are isolated from the memory B cells of a survivor of the 2003 outbreak and reveal a target for the rational design of pan-sarbecovirus vaccines.
References
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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
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UCSF Chimera--a visualization system for exploratory research and analysis.
Eric F. Pettersen,Thomas D. Goddard,Conrad C. Huang,Gregory S. Couch,Daniel M. Greenblatt,Elaine C. Meng,Thomas E. Ferrin +6 more
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Coot: model-building tools for molecular graphics.
Paul Emsley,Kevin Cowtan +1 more
TL;DR: CCP4mg is a project that aims to provide a general-purpose tool for structural biologists, providing tools for X-ray structure solution, structure comparison and analysis, and publication-quality graphics.
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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
TL;DR: Identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China, and it is shown that this virus belongs to the species of SARSr-CoV, indicates that the virus is related to a bat coronav virus.
Journal ArticleDOI
Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study
Nanshan Chen,Min Zhou,Xuan Dong,Jie-Ming Qu,Fengyun Gong,Yang Han,Yang Qiu,Jingli Wang,Ying Liu,Yuan Wei,Jia'an Xia,Ting Yu,Xinxin Zhang,Li Zhang +13 more
TL;DR: Characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia, and further investigation is needed to explore the applicability of the Mu LBSTA scores in predicting the risk of mortality in 2019-nCoV infection.
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