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
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Prolonged virus shedding even after seroconversion in a patient with COVID-19.
Wang Da Liu,Sui-Yuan Chang,Jann-Tay Wang,Ming Jui Tsai,Chien-Ching Hung,Chia-Lin Hsu,Shan-Chwen Chang +6 more
TL;DR: Viral detection from throat gargling sample could be an alternative diagnostic method for mild COVID-19 patients with scarce sputum andSputum remained the most sensitive specimen for viral detection after clinical symptoms resolved.
Journal ArticleDOI
Proteolytic Cleavage of the SARS-CoV-2 Spike Protein and the Role of the Novel S1/S2 Site.
TL;DR: This work investigates the potential role of this novel S1/S2 cleavage site and presents direct biochemical evidence for proteolytic processing by a variety of proteases in the context of the origin of SARS-CoV-2, viral stability and transmission.
Journal ArticleDOI
Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein.
Naveenchandra Suryadevara,Swathi Shrihari,Pavlo Gilchuk,Laura A. VanBlargan,Elad Binshtein,Seth J. Zost,Rachel S. Nargi,Rachel E. Sutton,Emma S. Winkler,Elaine C. Chen,Mallorie E. Fouch,Edgar Davidson,Benjamin J. Doranz,Rita E. Chen,Pei Yong Shi,Robert H. Carnahan,Larissa B. Thackray,Michael S. Diamond,James E. Crowe +18 more
TL;DR: In this article, a panel of human monoclonal antibodies binding to diverse epitopes on the N-terminal domain (NTD) of S protein from SARS-CoV-2 convalescent donors and found a minority of these possessed neutralizing activity.
Journal ArticleDOI
Comorbid Chronic Diseases and Acute Organ Injuries Are Strongly Correlated with Disease Severity and Mortality among COVID-19 Patients: A Systemic Review and Meta-Analysis
TL;DR: It is found that both acute cardiac injury and acute kidney injury are highly correlated with an increased risk of COVID-19-related mortality, and there is no correlation between chronic liver disease and increased disease severity.
Journal ArticleDOI
Conformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM.
Cong Xu,Cong Xu,Yanxing Wang,Caixuan Liu,Caixuan Liu,Chao Zhang,W. Han,W. Han,Xiaoyu Hong,Xiaoyu Hong,Yifan Wang,Yifan Wang,Qin Hong,Qin Hong,S. Wang,S. Wang,Qiaoyu Zhao,Qiaoyu Zhao,Yalei Wang,Yong Yang,Kaijian Chen,Kaijian Chen,Wei Zheng,Wei Zheng,Liangliang Kong,Fangfang Wang,Qinyu Zuo,Zhong Huang,Yao Cong,Yao Cong +29 more
TL;DR: The findings depict the mechanism of ACE2-induced S trimer conformational transitions from the ground prefusion state toward the postfusion state, facilitating development of anti–SARS-CoV-2 vaccines and therapeutics.
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
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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