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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Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2.
Qihui Wang,Yanfang Zhang,Lili Wu,Sheng Niu,Sheng Niu,Chunli Song,Chunli Song,Zengyuan Zhang,Guangwen Lu,Chengpeng Qiao,Yu Hu,Yu Hu,Kwok-Yung Yuen,Qisheng Wang,Huan Zhou,Jinghua Yan,Jianxun Qi +16 more
TL;DR: The crystal structure of the C-terminal domain of SARS-CoV-2 (SARS- coV- 2-CTD) spike (S) protein in complex with human ACE2 (hACE2) is presented, which reveals a hACE2-binding mode similar overall to that observed for SARS -CoV.
Journal ArticleDOI
Extrapulmonary manifestations of COVID-19.
Aakriti Gupta,Aakriti Gupta,Mahesh V. Madhavan,Kartik Sehgal,Kartik Sehgal,Nandini Nair,Shiwani Mahajan,Tejasav S. Sehrawat,Behnood Bikdeli,Behnood Bikdeli,Neha Ahluwalia,John C. Ausiello,Elaine Wan,Daniel E. Freedberg,Ajay J. Kirtane,Sahil A. Parikh,Mathew S. Maurer,Anna S. Nordvig,Domenico Accili,Joan M. Bathon,Sumit Mohan,Kenneth A. Bauer,Kenneth A. Bauer,Martin B. Leon,Harlan M. Krumholz,Nir Uriel,Mandeep R. Mehra,Mitchell S.V. Elkind,Mitchell S.V. Elkind,Gregg W. Stone,Allan Schwartz,David D. Ho,John P. Bilezikian,Donald W. Landry +33 more
TL;DR: The extrapulmonary organ-specific pathophysiology, presentations and management considerations for patients with COVID-19 are reviewed to aid clinicians and scientists in recognizing and monitoring the spectrum of manifestations, and in developing research priorities and therapeutic strategies for all organ systems involved.
Journal ArticleDOI
Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection.
Jennifer M. Dan,Jennifer M. Dan,Jose Mateus,Yu Kato,Kathryn M. Hastie,Esther Dawen Yu,Caterina E. Faliti,Alba Grifoni,Sydney I. Ramirez,Sydney I. Ramirez,Sonya Haupt,April Frazier,Catherine Nakao,Vamseedhar Rayaprolu,Stephen A. Rawlings,Bjoern Peters,Bjoern Peters,Florian Krammer,Viviana Simon,Erica Ollmann Saphire,Erica Ollmann Saphire,Davey M. Smith,Daniela Weiskopf,Alessandro Sette,Alessandro Sette,Shane Crotty,Shane Crotty +26 more
TL;DR: This article analyzed multiple compartments of circulating immune memory to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 254 samples from 188 COVID-19 cases, including 43 samples at ≥ 6 months after infection.
Journal ArticleDOI
Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates.
Edward E. Walsh,Robert W. Frenck,Ann R. Falsey,Ann R. Falsey,Nicholas Kitchin,Judith Absalon,Alejandra Gurtman,Stephen Lockhart,Kathleen M. Neuzil,Mark J. Mulligan,Ruth Bailey,Kena A. Swanson,Ping Li,Kenneth Koury,Warren Kalina,David A. Cooper,Camila R. Fontes-Garfias,Pei Yong Shi,Özlem Türeci,Tompkins Kristin Rachael,Kirsten E. Lyke,Vanessa Raabe,Philip R. Dormitzer,Kathrin U. Jansen,Ugur Sahin,William C. Gruber +25 more
TL;DR: The safety and immunogenicity data from this U.S. phase 1 trial of two vaccine candidates in younger and older adults support the selection of BNT162b2 for advancement to a pivotal phase 2–3 safety and efficacy evaluation.
Journal ArticleDOI
SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues.
Carly G. K. Ziegler,Samuel J. Allon,Sarah K. Nyquist,Ian M. Mbano,Vincent N. Miao,Constantine N. Tzouanas,Yuming Cao,Ashraf S. Yousif,Julia Bals,Blake M. Hauser,Blake M. Hauser,Jared Feldman,Jared Feldman,Christoph Muus,Christoph Muus,Marc H. Wadsworth,Samuel W. Kazer,Travis K. Hughes,Benjamin Doran,G. James Gatter,G. James Gatter,G. James Gatter,Marko Vukovic,Faith Taliaferro,Faith Taliaferro,Benjamin E. Mead,Zhiru Guo,Jennifer P. Wang,Delphine Gras,Magali Plaisant,Meshal Ansari,Ilias Angelidis,Heiko Adler,Jennifer M.S. Sucre,Chase J. Taylor,Brian M. Lin,Avinash Waghray,Vanessa Mitsialis,Vanessa Mitsialis,Daniel F. Dwyer,Kathleen M. Buchheit,Joshua A. Boyce,Nora A. Barrett,Tanya M. Laidlaw,Shaina L. Carroll,Lucrezia Colonna,Victor Tkachev,Victor Tkachev,Christopher W. Peterson,Christopher W. Peterson,Alison Yu,Alison Yu,Hengqi Betty Zheng,Hengqi Betty Zheng,Hannah P. Gideon,Caylin G. Winchell,Philana Ling Lin,Philana Ling Lin,Colin D. Bingle,Scott B. Snapper,Scott B. Snapper,Jonathan A. Kropski,Jonathan A. Kropski,Fabian J. Theis,Herbert B. Schiller,Laure-Emmanuelle Zaragosi,Pascal Barbry,Alasdair Leslie,Alasdair Leslie,Hans-Peter Kiem,Hans-Peter Kiem,JoAnne L. Flynn,Sarah M. Fortune,Sarah M. Fortune,Sarah M. Fortune,Bonnie Berger,Robert W. Finberg,Leslie S. Kean,Leslie S. Kean,Manuel Garber,Aaron G. Schmidt,Aaron G. Schmidt,Daniel Lingwood,Alex K. Shalek,Jose Ordovas-Montanes,Nicholas E. Banovich,Alvis Brazma,Tushar J. Desai,Thu Elizabeth Duong,Oliver Eickelberg,Christine S. Falk,Michael Farzan,Ian A. Glass,Muzlifah Haniffa,Peter Horvath,Deborah T. Hung,Naftali Kaminski,Mark A. Krasnow,Malte Kühnemund,Robert Lafyatis,Haeock Lee,Sylvie Leroy,Sten Linnarson,Joakim Lundeberg,Kerstin B. Meyer,Alexander V. Misharin,Martijn C. Nawijn,Marko Nikolic,Dana Pe'er,Joseph E. Powell,Stephen R. Quake,Jay Rajagopal,Purushothama Rao Tata,Emma L. Rawlins,Aviv Regev,Paul A. Reyfman,Mauricio Rojas,Orit Rosen,Kourosh Saeb-Parsy,Christos Samakovlis,Herbert B. Schiller,Joachim L. Schultze,Max A. Seibold,Douglas P. Shepherd,Jason R. Spence,Avrum Spira,Xin Sun,Sarah A. Teichmann,Fabian J. Theis,Alexander M. Tsankov,Maarten van den Berge,Michael von Papen,Jeffrey A. Whitsett,Ramnik J. Xavier,Yan Xu,Kun Zhang +135 more
TL;DR: The data suggest that SARS-CoV-2 could exploit species-specific interferon-driven upregulation of ACE2, a tissue-protective mediator during lung injury, to enhance infection.
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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