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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Molecular mechanism of interaction between SARS-CoV-2 and host cells and interventional therapy.
TL;DR: In this article, the authors reviewed the current knowledge and crucial information about how SARS-CoV-2 attaches on the surface of host cells through a variety of receptors, such as ACE2, neuropilin-1, AXL, and antibody-FcγR complexes.
Journal ArticleDOI
Body Localization of ACE-2: On the Trail of the Keyhole of SARS-CoV-2
TL;DR: The physiological body distribution, expression, and activities of ACE2 are mapped and its potential correlations and mutal interactions with the disparate symptoms present in SARS-CoV-2 patients at the level of different organs are discussed.
Journal ArticleDOI
Human angiotensin-converting enzyme 2 transgenic mice infected with SARS-CoV-2 develop severe and fatal respiratory disease.
Joseph W. Golden,Curtis R. Cline,Xiankun Zeng,Aura R. Garrison,Brian D. Carey,Eric M. Mucker,Lauren E. White,Joshua D. Shamblin,Rebecca L. Brocato,Jun Liu,April M. Babka,Hypaitia B. Rauch,Jeffrey M. Smith,Bradley S. Hollidge,Collin Fitzpatrick,Catherine V. Badger,Jay W. Hooper +16 more
TL;DR: To the authors' knowledge, this is the first highly lethal murine infection model for SARS-CoV-2 and should be valuable for the study of Sars-Cov-2 pathogenesis and for the assessment of MCMs.
Journal ArticleDOI
Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses.
Kevin O. Saunders,Esther J. Lee,Robert Parks,David R. Martinez,Dapeng Li,Haiyan Chen,Robert J. Edwards,Sophie M. C. Gobeil,Maggie Barr,Katayoun Mansouri,S. Munir Alam,Laura L. Sutherland,Fangping Cai,Aja Sanzone,Madison Berry,Kartik Manne,Kevin W. Bock,Mahnaz Minai,Bianca M. Nagata,Anyway B. Kapingidza,Mihai L. Azoitei,Longping V. Tse,Trevor Scobey,Rachel L. Spreng,R. Wes Rountree,C. Todd DeMarco,Thomas N. Denny,Christopher W. Woods,Elizabeth Petzold,Juanjie Tang,Thomas H. Oguin,Gregory D. Sempowski,Matthew Gagne,Daniel C. Douek,Mark A. Tomai,Christopher B. Fox,Robert A. Seder,Kevin Wiehe,Drew Weissman,Norbert Pardi,Hana Golding,Surender Khurana,Priyamvada Acharya,Hanne Leth Andersen,Mark G. Lewis,Ian N. Moore,David C. Montefiori,Ralph S. Baric,Barton F. Haynes +48 more
TL;DR: The authors showed that immunization of macaques with nanoparticles conjugated with the receptor-binding domain of SARS-CoV-2, and adjuvanted with 3M-052 and alum, elicits cross-neutralizing antibody responses against bat coronaviruses, SARS, CoV and SARS CoV2.
Journal ArticleDOI
Characterizations of SARS-CoV-2 mutational profile, spike protein stability and viral transmission.
Sayantan Laha,Joyeeta Chakraborty,Shantanab Das,Soumen K. Manna,Sampa Biswas,Raghunath Chatterjee +5 more
TL;DR: Analysis of protein structure stability of surface glycoprotein mutants indicated the viability of specific variants and are more prone to be temporally and spatially distributed across the globe.
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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