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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ACE2 receptor polymorphism: Susceptibility to SARS-CoV-2, hypertension, multi-organ failure, and COVID-19 disease outcome.
TL;DR: The relationship between the virus, the peptidase function of ACE2 and the levels of angiotensin II in SARS-CoV-2 infected patients should help to better understand the pathophysiology of the disease and the multi-organ failures observed in severe COVID-19 cases, particularly heart failure.
Journal ArticleDOI
Distinct antibody responses to SARS-CoV-2 in children and adults across the COVID-19 clinical spectrum.
Stuart P. Weisberg,Thomas J. Connors,Yun Zhu,Matthew R. Baldwin,Wen-Hsuan W. Lin,Sandeep N. Wontakal,Peter A. Szabo,Steven B. Wells,Pranay Dogra,Joshua I. Gray,Emma Idzikowski,Debora Stelitano,Debora Stelitano,Francesca T. Bovier,Francesca T. Bovier,Julia Davis-Porada,Rei Matsumoto,Maya Meimei Li Poon,Michael Chait,Cyrille Mathieu,Branka Horvat,Didier Decimo,Krystalyn E. Hudson,Flavia Dei Zotti,Zachary C. Bitan,Francesca La Carpia,Stephen A. Ferrara,Emily M. Mace,Joshua D. Milner,Anne Moscona,Eldad A. Hod,Matteo Porotto,Matteo Porotto,Donna L. Farber +33 more
TL;DR: In this paper, the authors show distinct antibody responses in children and adults after SARS-CoV-2 infection, indicating a distinct infection course and immune response in children independent of whether they develop multisystem inflammatory syndrome (MIS-C).
Journal ArticleDOI
A Single-Dose Intranasal ChAd Vaccine Protects Upper and Lower Respiratory Tracts against SARS-CoV-2.
Ahmed O. Hassan,Natasha M. Kafai,Igor P. Dmitriev,Julie M. Fox,Brittany K. Smith,Ian B. Harvey,Rita E. Chen,Emma S. Winkler,Alex W. Wessel,James Brett Case,Elena A. Kashentseva,Broc T. McCune,Adam L. Bailey,Haiyan Zhao,Laura A. VanBlargan,Ya Nan Dai,Meisheng Ma,Lucas J. Adams,Swathi Shrihari,Jonathan E. Danis,Lisa E. Gralinski,Yixuan J. Hou,Alexandra Schäfer,Arthur S. Kim,Shamus P. Keeler,Daniela Weiskopf,Ralph S. Baric,Michael J. Holtzman,Daved H. Fremont,David T. Curiel,Michael S. Diamond +30 more
TL;DR: Intranasal administration of a chimpanzee adenovirus-vectored vaccine encoding a pre-fusion stabilized spike protein is a candidate for preventing SARS-CoV-2 infection and transmission, and curtailing pandemic spread.
Journal ArticleDOI
Soluble angiotensin-converting enzyme 2: a potential approach for coronavirus infection therapy?
TL;DR: It is timely to explain the connection between the SARS-CoV, SARS -CoV-2, ACE2 and the rationale for soluble ACE2 as a potential therapy and the link to the 2003 SARS epidemic is explained.
Journal ArticleDOI
Durability of mRNA-1273 vaccine-induced antibodies against SARS-CoV-2 variants.
Pegu, Amarendra, O’Connell, Sarah E.,Stephen D. Schmidt,O’Dell, Sijy, Talana, Chloe A.,Flach, Britta, Jackson, Lisa, Leav, Brett, Ledgerwood, Julie E.,Catherine J. Luke,Makowski, Mat, Nason, Martha C.,Paul C. Roberts,Roederer, Mario, Rebolledo, Paulina A. +7 more
TL;DR: In this article, the authors assess the impact of SARS-CoV-2 variants B.1.7 (Alpha), B.351 (Beta), P.1, 1.429 (Epsilon), B1.526 (Iota), and B.2 (Delta) on binding, neutralizing, and ACE2-competing antibodies elicited by the vaccine mRNA-1273 over seven months.
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.
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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
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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