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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Site-specific N-glycosylation Characterization of Recombinant SARS-CoV-2 Spike Proteins.
Yong Zhang,Wanjun Zhao,Yonghong Mao,Yaohui Chen,Shisheng Wang,Yi Zhong,Tao Su,Meng Gong,Dan Du,Xiaofeng Lu,Jingqiu Cheng,Hao Yang +11 more
TL;DR: The results revealed that the glycan types were highly determined by the differential processing of N-glycans among human and insect cells, regardless of the glycosites’ location, and the N- glycan compositions were conserved among different sizes of subunits.
Posted ContentDOI
Potent Neutralizing Monoclonal Antibodies Directed to Multiple Epitopes on the SARS-CoV-2 Spike
Lihong Liu,Pengfei Wang,Manoj S. Nair,Jian Yu,Micah Rapp,Qian Wang,Yang Luo,Jasper Fuk-Woo Chan,Vincent Sahi,Amir Figueroa,Xinzheng V. Guo,Gabriele Cerutti,Jude Bimela,Jason Gorman,Tongqing Zhou,Zhiwei Chen,Zhiwei Chen,Kwok-Yung Yuen,Peter D. Kwong,Peter D. Kwong,Joseph Sodroski,Michael T. Yin,Zizhang Sheng,Zizhang Sheng,Yaoxing Huang,Lawrence Shapiro,Lawrence Shapiro,David D. Ho +27 more
TL;DR: In this article, the authors reported the isolation of 61 SARS-CoV-2-neutralizing monoclonal antibodies from 5 infected patients hospitalized with severe disease among these are 19 antibodies that potently neutralized the authentic SARS CoV2 in vitro, 9 of which exhibited exquisite potency, with 50% virus-inhibitory concentrations of 1 to 9 ng/mL Epitope mapping showed this collection of 19 antibodies to be about equally divided between those directed to the receptor-binding domain (RBD) and those to the Nterminal domain (NT
Journal ArticleDOI
Inference of person-to-person transmission of COVID-19 reveals hidden super-spreading events during the early outbreak phase
Liang Wang,Xavier Didelot,Jing Yang,Gary Wong,Gary Wong,Yi Shi,Wenjun Liu,George F. Gao,Yuhai Bi,Yuhai Bi +9 more
TL;DR: The results showed that super-spreading events played an important role in the early stage of the COVID-19 outbreak, indicating there are individuals who directly infected a disproportionately large number of people.
Journal ArticleDOI
Identifying SARS-CoV-2 Entry Inhibitors through Drug Repurposing Screens of SARS-S and MERS-S Pseudotyped Particles
Catherine Z. Chen,Miao Xu,Manisha Pradhan,Kirill Gorshkov,Jennifer D. Petersen,Marco R. Straus,Wei Zhu,Paul Shinn,Hui Guo,Min Shen,Carleen Klumpp-Thomas,Samuel G. Michael,Joshua Zimmerberg,Wei Zheng,Gary R. Whittaker +14 more
TL;DR: Six compounds were discovered to be broad spectrum inhibitors for spike-mediated entry and could contribute to the development of effective treatments against the initial stage of viral infection and provide mechanistic information that might aid the design of new drug combinations for clinical trials for COVID-19 patients.
Journal ArticleDOI
Human soluble ACE2 improves the effect of remdesivir in SARS-CoV-2 infection.
Vanessa Monteil,Matheus Dyczynski,Volker M. Lauschke,Hyesoo Kwon,Gerald Wirnsberger,Sonia Youhanna,Haibo Zhang,Arthur S. Slutsky,Carmen Hurtado del Pozo,Moritz Horn,Nuria Montserrat,Josef M. Penninger,Josef M. Penninger,Ali Mirazimi,Ali Mirazimi +14 more
TL;DR: The data provided here demonstrate that combining two therapeutic modalities with different targets, common strategy in HIV treatment, exhibit strong additive effects at sub‐toxic concentrations, and lay the groundwork for the study of combinatorial regimens in future COVID‐19 clinical trials.
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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