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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SARS-CoV-2 Infection Depends on Cellular Heparan Sulfate and ACE2.
Thomas Mandel Clausen,Thomas Mandel Clausen,Thomas Mandel Clausen,Daniel R. Sandoval,Charlotte B Spliid,Charlotte B Spliid,Charlotte B Spliid,Jessica Pihl,Jessica Pihl,Jessica Pihl,Hailee R. Perrett,Chelsea D. Painter,Anoop Narayanan,Sydney A. Majowicz,Elizabeth M. Kwong,Rachael N. McVicar,Bryan E. Thacker,Charles A. Glass,Zhang Yang,Jonathan L. Torres,Gregory J. Golden,Phillip L. Bartels,Ryan N. Porell,Aaron F. Garretson,Logan K. Laubach,Jared Feldman,Xin Yin,Yuan Pu,Blake M. Hauser,Timothy M. Caradonna,Benjamin P. Kellman,Cameron Martino,Philip L.S.M. Gordts,Sumit K. Chanda,Aaron G. Schmidt,Aaron G. Schmidt,Kamil Godula,Sandra L Leibel,Joyce Jose,Kevin D. Corbett,Andrew B. Ward,Aaron F. Carlin,Jeffrey D. Esko +42 more
TL;DR: A model in which viral attachment and infection involves heparan sulfate-dependent enhancement of binding to ACE2 is suggested, in which Manipulation of hepara sulfate or inhibition of viral adhesion by exogenous heparin presents new therapeutic opportunities.
Journal ArticleDOI
Viral targets for vaccines against COVID-19.
Lianpan Dai,George F. Gao +1 more
TL;DR: In this article, the authors discuss which viral elements are used in COVID-19 vaccine candidates, why they might act as good targets for the immune system and the implications for protective immunity.
Journal ArticleDOI
Insights into SARS-CoV-2 genome, structure, evolution, pathogenesis and therapies: Structural genomics approach.
Ahmad Abu Turab Naqvi,Kisa Fatima,Taj Mohammad,Urooj Fatima,Indrakant K. Singh,Archana Singh,Shaikh M. Atif,Gururao Hariprasad,Gulam Mustafa Hasan,Imtaiyaz Hassan +9 more
TL;DR: The analysis suggests a minimal variation in the genome sequence of SARS-CoV-2, may be responsible for a drastic change in the structures of target proteins, makes available drugs ineffective.
Journal ArticleDOI
Preexisting and de novo humoral immunity to SARS-CoV-2 in humans
Kevin W. Ng,Nikhil Faulkner,Georgina H. Cornish,Annachiara Rosa,Ruth Harvey,Saira Hussain,Rachel Ulferts,Christopher Earl,A.G. Wrobel,D.J. Benton,Chloe Roustan,William Bolland,Rachael Thompson,Ana Agua-Doce,Philip Hobson,Judith Heaney,Hannah Rickman,Stavroula Paraskevopoulou,Catherine F Houlihan,Kirsty Thomson,Emilie Sanchez,Gee Yen Shin,Moira J. Spyer,Dhira Joshi,Nicola O’Reilly,Philip A. Walker,Svend Kjaer,Andrew Riddell,Catherine Moore,Bethany R. Jebson,Meredyth G. Ll Wilkinson,Lucy R. Marshall,Elizabeth C. Rosser,Anna Radziszewska,Hannah Peckham,Coziana Ciurtin,Lucy R. Wedderburn,Rupert Beale,Charles Swanton,Sonia Gandhi,Brigitta Stockinger,John W. McCauley,Steve Gamblin,Laura E. McCoy,Peter Cherepanov,Eleni Nastouli,George Kassiotis,George Kassiotis +47 more
TL;DR: Using diverse assays for antibodies recognizing SARS-CoV-2 proteins, preexisting humoral immunity was detected and antibodies targeting the S2 subunit were particularly prevalent in children and adolescents.
Journal ArticleDOI
SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses
Wanwisa Dejnirattisai,Jiandong Huo,D. Zhou,Jiří Zahradník,P Supasa,Changxiao Liu,Helen M. E. Duyvesteyn,Helen M. Ginn,Alexander J. Mentzer,Aekkachai Tuekprakhon,Rungtiwa Nutalai,Beibei Wang,Aiste Dijokaite,Suman Khan,Ori Avinoam,M.W. Bahar,Donal T. Skelly,S Adele,Síle A. Johnson,Thomas G Ritter,Chris Jb Mason,Christina Dold,Daniel Pan,Sara Assadi,A. Bellass,Nikki Omo-Dare,David Koeckerling,Amy Flaxman,D Jenkin,Parvinder K. Aley,Merryn Voysey,Sue Ann Costa Clemens,Felipe Gomes Naveca,Valdinete Alves do Nascimento,Fernanda Nascimento,Cristiano Fernandes da Costa,Paola Cristina Resende,Alex Pauvolid-Corrêa,Marilda M. Siqueira,Vicky L. Baillie,Natali Serafin,Gaurav Kwatra,Kelly Da Silva,Shabir A. Madhi,Marta C. Nunes,Tariq Mehmood Malik,Peter J. M. Openshaw,J Kenneth Baillie,Malcolm G Semple,Alain Townsend,Kuan-Ying A. Huang,Tiong Kit Tan,Miles W. Carroll,Paul Klenerman,Eleanor Barnes,Susanna Dunachie,Bede Constantinides,Hermione J. Webster,Derrick W. Crook,Andrew J. Pollard,Teresa Lambe,Neil G. Paterson,Mark Williams,Elizabeth E. Fry,Juthathip Mongkolsapaya,Jingshan Ren,Gideon Schreiber,David Stuart,Gavin R. Screaton +68 more
TL;DR: In this article , a new SARS-CoV-2 viral isolate Omicron-B.1.529 was announced, containing far more mutations in Spike (S) than previously reported variants, leading to a large number of mutations in the ACE2 binding site and rebalances receptor affinity to that of earlier pandemic viruses.
References
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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.
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