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
The SARS-CoV-2 Exerts a Distinctive Strategy for Interacting with the ACE2 Human Receptor.
TL;DR: This work compares the interaction between the human ACE2 receptor and the SARS-CoV-2 spike protein with that of other pathogenic coronaviruses using molecular dynamics simulations and postulates that the versatility of cell receptor binding strategies has immediate implications for therapeutic strategies.
Posted ContentDOI
BNT162b2 induces SARS-CoV-2-neutralising antibodies and T cells in humans
Ugur Sahin,Alexander Muik,Isabel Vogler,Evelyna Derhovanessian,Lena M. Kranz,Mathias Vormehr,Jasmin Quandt,Nicole Bidmon,Alexander Ulges,Alina Baum,Kristen E. Pascal,Daniel Maurus,Sebastian Brachtendorf,Verena L Loerks,Julian Sikorski,Peter Koch,Rolf Hilker,Dirk Becker,Ann-Kathrin Eller,Jan Gruetzner,Manuel Tonigold,Carsten Boesler,Corinna Rosenbaum,Ludwig Heesen,Marie-Cristine Kuehnle,Asaf Poran,Jesse Z. Dong,Ulrich Luxemburger,Alexandra Kemmer-Brueck,David J. Langer,Martin Bexon,Stefanie Bolte,Tania Palanche,Armin Schultz,Sybille Baumann,Azita J. Mahiny,Gábor Boros,Jonas Reinholz,Gabor T Szabo,Katalin Karikó,Pei Yong Shi,Camila R. Fontes-Garfias,John L. Perez,Mark Cutler,David A. Cooper,Christos A. Kyratsous,Philip R. Dormitzer,Kathrin U. Jansen,Oezlem Tuereci +48 more
TL;DR: Vaccination with BNT162b2 at well tolerated doses elicits a combined adaptive humoral and cellular immune response, which together may contribute to protection against COVID-19.
Journal ArticleDOI
A novel rapid detection for SARS-CoV-2 spike 1 antigens using human angiotensin converting enzyme 2 (ACE2).
Jong Hwan Lee,Minsuk Choi,Yu-Jin Jung,Sung Kyun Lee,Chang-Seop Lee,Jung Kim,Jongwoo Kim,Nam Hoon Kim,Bum Tae Kim,Hong Gi Kim +9 more
TL;DR: This is the first study to detect SARS-CoV-2 S1 antigen using an LFIA with matched pair consisting of ACE2 and antibody, which can form matched pairs with commercially available antibodies.
Journal ArticleDOI
Comparison of Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein Binding to ACE2 Receptors from Human, Pets, Farm Animals, and Putative Intermediate Hosts.
Xiaofeng Zhai,Jiumeng Sun,Ziqing Yan,Jie Zhang,Jin Zhao,Zongzheng Zhao,Qi Gao,Wan Ting He,Michael Veit,Shuo Su +9 more
TL;DR: X-ray structures of human ACE2 bound to the receptor-binding domain (RBD) of the spike protein (S) from SARS-CoV-2 are used to predict its binding to ACE2 proteins from different animals, including pets, farm animals, and putative intermediate hosts of Sars-Cov-2, and it is found that ACE2 from species known to support SATS infection tolerate many amino acid changes, indicating that the species barrier might be low.
Journal ArticleDOI
Design of Potent Membrane Fusion Inhibitors against SARS-CoV-2, an Emerging Coronavirus with High Fusogenic Activity.
TL;DR: This study verified that SARS-CoV-2 uses human angiotensin-converting enzyme 2 (ACE2) as a cell receptor and that its spike (S) protein mediates high membrane fusion activity, and designed an HR2 sequence-based lipopeptide fusion inhibitor, termed IPB02, which showed highly potent activities in inhibiting Sars-Cov-2 S protein-mediated cell-cell fusion and pseudovirus transduction.
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