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
More filters
Journal ArticleDOI
Structure-guided multivalent nanobodies block SARS-CoV-2 infection and suppress mutational escape.
Paul-Albert Koenig,Hrishikesh Das,Hejun Liu,Beate M. Kümmerer,Florian N. Gohr,Lea-Marie Jenster,Lisa D. J. Schiffelers,Yonas M. Tesfamariam,Miki Uchima,Jennifer Deborah Wuerth,Karl Gatterdam,Natalia Ruetalo,Maria H Christensen,Caroline I. Fandrey,Sabine Normann,Jan M. P. Tödtmann,Steffen Pritzl,Leo Hanke,Jannik Boos,Meng Yuan,Xueyong Zhu,Jonathan L. Schmid-Burgk,Hiroki Kato,Michael Schindler,Ian A. Wilson,Matthias Geyer,Kerstin U. Ludwig,B. Martin Hallberg,Nicholas C. Wu,Florian I. Schmidt +29 more
TL;DR: In this paper, the authors used x-ray crystallography and cryo-electron microscopy to define two distinct binding epitopes of the SARS-CoV-2 spike protein.
Journal ArticleDOI
SARS-CoV-2 proteome microarray for global profiling of COVID-19 specific IgG and IgM responses
He wei Jiang,Yang Li,Hai nan Zhang,Wei Wang,Xiao Yang,Huan Qi,Hua Li,Dong Men,Jie Zhou,Sheng-Ce Tao +9 more
TL;DR: A systemic view of the SARS-CoV-2 specific IgG and IgM responses is presented and provides insights to aid the development of effective diagnostic, therapeutic and vaccination strategies.
Journal ArticleDOI
Tackling COVID-19 with neutralizing monoclonal antibodies
TL;DR: An overview of SARS-CoV-2-neutralizing mAbs, including their origin, specificity, structure, antiviral and immunological mechanisms of action, and resistance to circulating variants, as well as a snapshot of the clinical trials of approved or late-stage mAb therapeutics can be found in this paper.
Journal ArticleDOI
Molecular diagnostic technologies for COVID-19: Limitations and challenges.
TL;DR: An overview of the commercial and pre-commercial molecular diagnostics to address several questions and issues related to the limitations of current technologies and future research and development challenges to enable timely, rapid, low-cost, and accurate diagnosis of emerging infectious diseases.
Journal ArticleDOI
Aging, Immunity, and COVID-19: How Age Influences the Host Immune Response to Coronavirus Infections?
Varnica Bajaj,Varnica Bajaj,Nirupa Gadi,Nirupa Gadi,Allison P. Spihlman,Allison P. Spihlman,Samantha C. Wu,Samantha C. Wu,Christopher H. Choi,Christopher H. Choi,Vaishali R. Moulton +10 more
TL;DR: In this article, age-related quantitative and qualitative changes in the immune system affect cells and soluble mediators of both the innate and adaptive immune responses within lymphoid and non-lymphoid peripheral tissues.
References
More filters
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.
Related Papers (5)
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
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