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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Human ACE2 receptor polymorphisms and altered susceptibility to SARS-CoV-2.
Kushal Suryamohan,Devan Diwanji,Eric Stawiski,Ravi Gupta,Shane Miersch,Jiang Liu,Chao Chen,Ying-Ping Jiang,Frederic A. Fellouse,J. Fah Sathirapongsasuti,Patrick K. Albers,Tanneeru Deepak,Reza Saberianfar,Aakrosh Ratan,Gavin Washburn,Monika Mis,Devi Santhosh,Sneha Somasekar,G. H. Hiranjith,Derek Vargas,Sangeetha Mohan,Sameer Phalke,Boney Kuriakose,Aju Antony,Mart Ustav,Stephan C. Schuster,Sachdev S. Sidhu,Jagath Reddy Junutula,Natalia Jura,Somasekar Seshagiri +29 more
TL;DR: In this article, the authors assessed if ACE2 polymorphisms can alter host susceptibility to SARS-CoV-2 by affecting this interaction and found that soluble ACE2 K26R and T92I were more effective in blocking entry of S-protein pseudotyped virus.
Journal ArticleDOI
Antibody-mediated broad sarbecovirus neutralization through ACE2 molecular mimicry
Young-Jun Park,Anna De Marco,Tyler N. Starr,Zhuoming Li,Dora Pinto,Alexandra C. Walls,Fabrizia Zatta,Samantha K. Zepeda,John E. Bowen,Kaitlin R. Sprouse,Anshu Joshi,Martina Giurdanella,Barbara Guarino,Julia Noack,Rana Abdelnabi,Shi Yan Caroline Foo,Laura E. Rosen,Florian A. Lempp,Fabio Benigni,Gyorgy Snell,Johan Neyts,Sean P. J. Whelan,Herbert W. Virgin,Jesse D. Bloom,Davide Corti,Matteo Samuele Pizzuto,David Veesler +26 more
TL;DR: The isolation and characterization of a human monoclonal antibody, designated S2K146, that broadly neutralizes viruses belonging to SARS-CoV– and SARV-2–related sarbecovirus clades, which use angiotensin-converting enzyme 2 (ACE2) as an entry receptor.
Journal ArticleDOI
Remdesivir in the treatment of coronavirus disease 2019 (COVID-19): a simplified summary.
TL;DR: This commentary has portrayed the structure of the coronavirus in a simple way as well as the site where remdesivir acts, and displayed the ongoing clinical trials, aswell as a published study that was conducted on compassionate base.
Journal ArticleDOI
SARS-CoV-2 Antibody Responses Are Correlated to Disease Severity in COVID-19 Convalescent Individuals.
Cecilie Bo Hansen,Ida Jarlhelt,Laura Pérez-Alós,Lone H. Landsy,Mette Loftager,Anne Rosbjerg,Charlotte Helgstrand,Jais Rose Bjelke,Thomas Egebjerg,Joseph G. Jardine,Charlotte Sværke Jørgensen,Kasper Iversen,Rafael Bayarri-Olmos,Peter Garred,Mikkel-Ole Skjoedt +14 more
TL;DR: It is shown that the IgM, A, and G Ab responses against receptor-binding domain are significantly correlated to the disease severity, and these assays and the data generated from them are highly relevant for diagnostics and prognostics and contribute to the understanding of long-term COVID-19 immunity.
Posted ContentDOI
The SARS-CoV-2 receptor ACE2 expression of maternal-fetal interface and fetal organs by single cell transcriptome study
TL;DR: The authors have withdrawn their manuscript whilst they perform additional experiments and analysis to test some of their conclusions further, and the authors do not wish this work to be cited as reference for the project.
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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Journal ArticleDOI
Coot: model-building tools for molecular graphics.
Paul Emsley,Kevin Cowtan +1 more
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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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