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
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Novel insights on the pulmonary vascular consequences of covid-19.
François Potus,Vicky Mai,Marius Lebret,Simon Malenfant,Emilie Breton-Gagnon,Annie C. Lajoie,Olivier Boucherat,Sébastien Bonnet,Steeve Provencher +8 more
TL;DR: The present article reviews the molecular factors shared by coronavirus infection and pulmonary vasculature defects, and the clinical relevance of pulmonary vascular alterations in the context of COVID-19.
Journal ArticleDOI
Interaction of the spike protein RBD from SARS-CoV-2 with ACE2: Similarity with SARS-CoV, hot-spot analysis and effect of the receptor polymorphism.
Houcemeddine Othman,Zied Bouslama,Jean-Tristan Brandenburg,Jorge da Rocha,Yosr Hamdi,Kais Ghedira,Najet Srairi-Abid,Scott Hazelhurst +7 more
TL;DR: An insight into the interaction of the viral spike Receptor Binding Domain (RBD) from different coronavirus isolates with host ACE2 protein is provided and corroborates the opinion that the interface segment of the spike protein RBD might be acquired by SARS-CoV-2 via a complex evolutionary process rather than a progressive accumulation of mutations.
Journal ArticleDOI
SARS-CoV-2 evolution in an immunocompromised host reveals shared neutralization escape mechanisms.
Sarah A. Clark,Lars Clark,Junhua Pan,Adrian Coscia,Lindsay G. A. McKay,Sundaresh Shankar,Rebecca I. Johnson,Vesna Brusic,Manish Chandra Choudhary,James Regan,Jonathan Z. Li,Anthony Griffiths,Jonathan Abraham +12 more
TL;DR: In this article, mutations occurring during virus evolution in a persistently infected immunocompromised individual were found to confer resistance to a common class of SARS-CoV-2 neutralizing antibodies they isolated from a healthy COVID-19 convalescent donor.
Posted ContentDOI
SARS-CoV-2 mRNA Vaccine Development Enabled by Prototype Pathogen Preparedness
Kizzmekia S. Corbett,Darin K. Edwards,Sarah R. Leist,Olubukola M. Abiona,Seyhan Boyoglu-Barnum,Rebecca A. Gillespie,Sunny Himansu,Alexandra Schäfer,Cynthia T. Ziwawo,Anthony T. DiPiazza,Kenneth H. Dinnon,Sayda Elbashir,Christine A. Shaw,Angela Woods,Ethan J. Fritch,David R. Martinez,Kevin W. Bock,Mahnaz Minai,Bianca M. Nagata,Geoffrey B. Hutchinson,Kapil Bahl,Dario Garcia-Dominguez,LingZhi Ma,Isabella Renzi,Wing-Pui Kong,Stephen D. Schmidt,Lingshu Wang,Yi Zhang,Laura J. Stevens,Emily Phung,Lauren A. Chang,Rebecca J. Loomis,Nedim Emil Altaras,Elisabeth Narayanan,Mihir Metkar,Vladimir Presnyak,Catherine Liu,Mark K. Louder,Wei Shi,Kwanyee Leung,Eun Sung Yang,Ande West,Kendra Gully,Nianshuang Wang,Daniel Wrapp,Nicole A. Doria-Rose,Guillaume Stewart-Jones,Hamilton Bennett,Martha Nason,Tracy J. Ruckwardt,Jason S. McLellan,Mark R. Denison,James D. Chappell,Ian N. Moore,Kaitlyn M. Morabito,John R. Mascola,Ralph S. Baric,Andrea Carfi,Barney S. Graham +58 more
TL;DR: It is shown that mRNA-1273 induces both potent neutralizing antibody and CD8 T cell responses and protects against SARS-CoV-2 infection in lungs and noses of mice without evidence of immunopathology.
Posted ContentDOI
Investigation of ACE2 N-terminal fragments binding to SARS-CoV-2 Spike RBD
Genwei Zhang,Sebastian Pomplun,Alexander R. Loftis,Xuyu Tan,Andrei Loas,Bradley L. Pentelute,Bradley L. Pentelute +6 more
TL;DR: Peptide-based binders are an attractive solution to inhibit the RBD-ACE2 interaction by adequately covering the extended protein contact interface and competitive BLI assays showed SBP1 does not outcompete ACE2 binding to Sino Biological insect-derived SARS-CoV-2-RBD protein variants.
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
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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
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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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