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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Characterisation of the transcriptome and proteome of SARS-CoV-2 reveals a cell passage induced in-frame deletion of the furin-like cleavage site from the spike glycoprotein.
Andrew D. Davidson,Maia Kavanagh Williamson,Sebastian D Lewis,Deborah K. Shoemark,Miles W. Carroll,Kate J. Heesom,Maria Zambon,Joanna Ellis,Philip A. Lewis,Julian A. Hiscox,Julian A. Hiscox,David A. Matthews +11 more
TL;DR: In this paper, the authors used direct RNA sequencing to determine the transcriptome of SARS-CoV-2 grown in Vero E6 cells which is widely used to propagate the novel coronavirus.
Journal ArticleDOI
SARS-CoV-2 spike D614G change enhances replication and transmission.
Bin Zhou,Tran Thi Nhu Thao,Donata Hoffmann,Adriano Taddeo,Nadine Ebert,Fabien Labroussaa,Anne Pohlmann,Jacqueline King,Silvio Steiner,Jenna N. Kelly,Jasmine Portmann,Nico Joel Halwe,Lorenz Ulrich,Bettina Salome Trüeb,Xiaoyu Fan,Bernd Hoffmann,Li Wang,Lisa Thomann,Xudong Lin,Hanspeter Stalder,Berta Pozzi,Simone de Brot,Nannan Jiang,Dan Cui,Jaber Hossain,Malania M. Wilson,Matthew W. Keller,Thomas J. Stark,John R. Barnes,Ronald Dijkman,Joerg Jores,Charaf Benarafa,David E. Wentworth,Volker Thiel,Martin Beer +34 more
TL;DR: In this paper, the authors used isogenic SARS-CoV-2 variants to demonstrate that the variant that contains S(D614G) has enhanced binding to the human cell-surface receptor angiotensin-converting enzyme (ACE2) and increased replication in primary human bronchial and nasal airway epithelial cultures as well as in a human ACE2 knock-in mouse model.
Journal ArticleDOI
Cross-reactive Antibody Response between SARS-CoV-2 and SARS-CoV Infections.
Huibin Lv,Nicholas C. Wu,Owen Tak-Yin Tsang,Meng Yuan,Ranawaka A.P.M. Perera,Wai Shing Leung,Ray T.Y. So,Jacky Man Chun Chan,Garrick K. Yip,Thomas Shiu Hong Chik,Yiquan Wang,Chris Yau Chung Choi,Yihan Lin,Wilson W. Ng,Jincun Zhao,Leo L.M. Poon,J S Malik Peiris,Ian A. Wilson,Chris Ka Pun Mok +18 more
TL;DR: Analysis of plasma from patients infected by SARS-CoV-2 or SARV, and from infected or immunized mice shows cross-reactivity in antibody binding to the spike protein is common, but cross-neutralization of the live viruses may be rare, indicating the presence of non-neutralizing antibody response to conserved epitopes in the spike.
Journal ArticleDOI
Potent SARS-CoV-2 neutralizing antibodies directed against spike N-terminal domain target a single supersite.
Gabriele Cerutti,Yicheng Guo,Tongqing Zhou,Jason Gorman,Myungjin Lee,Micah Rapp,Eswar R. Reddem,Jian Yu,Fabiana Bahna,Jude Bimela,Yaoxing Huang,Phinikoula S. Katsamba,Lihong Liu,Manoj S. Nair,Reda Rawi,Adam S. Olia,Pengfei Wang,Baoshan Zhang,Gwo-Yu Chuang,David D. Ho,Zizhang Sheng,Peter D. Kwong,Peter D. Kwong,Lawrence Shapiro +23 more
TL;DR: In this article, the NTD-directed neutralizing antibody targets a single supersite, formed primarily by a mobile β-hairpin and several flexible loops, and the largest glycan-free surface of NTD facing away from the viral membrane.
Journal ArticleDOI
COVID-19, immune system response, hyperinflammation and repurposing antirheumatic drugs
TL;DR: To gain better information about appropriate anti-inflammatory treatments, mostly used in rheumatology for COVID-19, the attention is focused on the structural features of Sars-CoV-2, the host immune response against SARS-Cov-2 and its association with the cytokine storm.
References
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Journal ArticleDOI
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
TL;DR: The epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of patients with laboratory-confirmed 2019-nCoV infection in Wuhan, China, were reported.
Journal ArticleDOI
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
TL;DR: Two unusual extensions are presented: Multiscale, which adds the ability to visualize large‐scale molecular assemblies such as viral coats, and Collaboratory, which allows researchers to share a Chimera session interactively despite being at separate locales.
Journal ArticleDOI
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.
Journal ArticleDOI
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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