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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Neutralization potency of monoclonal antibodies recognizing dominant and subdominant epitopes on SARS-CoV-2 Spike is impacted by the B.1.1.7 variant.
Carl Graham,Jeffrey Seow,Isabella Huettner,Hataf Khan,Neophytos Kouphou,Sam Acors,Helena Winstone,Suzanne Pickering,Rui Pedro Galão,Liane Dupont,Maria Jose Lista,Jose M. Jimenez-Guardeño,Adam Laing,Yin Wu,Yin Wu,Magdalene Joseph,Magdalene Joseph,Luke Muir,Marit J. van Gils,Weng M Ng,Helen M. E. Duyvesteyn,Yuguang Zhao,Thomas A. Bowden,Manu Shankar-Hari,Annachiara Rosa,Peter Cherepanov,Laura E. McCoy,Adrian Hayday,Adrian Hayday,Stuart J. D. Neil,Michael H. Malim,Katie J. Doores +31 more
TL;DR: In this article, the SARS-CoV-2 Spike receptor binding domain (RBD) and N-terminal domain (NTD) and S2 subunits of Spike were identified as the dominant targets for neutralizing antibodies.
Journal ArticleDOI
Amantadine disrupts lysosomal gene expression: A hypothesis for COVID19 treatment.
TL;DR: It is hypothesized that amantadine could decrease the viral load in SARS-CoV-2 positive patients and as such it may serve as a potent therapeutic decreasing the replication and infectivity of the virus likely leading to better clinical outcomes.
Journal ArticleDOI
Changes of hematological and immunological parameters in COVID-19 patients.
Xiaohong Yuan,Wanling Huang,Bing Ye,Cunrong Chen,Rongfeng Huang,Feng Wu,Qin Wei,Wei Zhang,Jianda Hu +8 more
TL;DR: The findings suggest that the lymphocyte counts, red blood cell counts and the immunoglobulin G antibodies of COVID-19 patients were impaired to varying degrees and the blood was in a state of hypercoagulation, which were more obvious in critically ill patients.
Journal ArticleDOI
Elicitation of broadly protective sarbecovirus immunity by receptor-binding domain nanoparticle vaccines.
Alexandra C. Walls,Marcos C. Miranda,Alexandra Schäfer,Minh N. Pham,Allison J. Greaney,Allison J. Greaney,Prabhu S. Arunachalam,Mary-Jane Navarro,M. Alejandra Tortorici,M. Alejandra Tortorici,Kenneth A. Rogers,Megan A. O'Connor,Lisa Shirreff,Douglas E. Ferrell,John E. Bowen,Natalie Brunette,Elizabeth Kepl,Samantha K Zepeda,Tyler N. Starr,Ching-Lin Hsieh,Brooke Fiala,Samuel Wrenn,Deleah Pettie,Claire Sydeman,Kaitlin R. Sprouse,Max Johnson,Alyssa Blackstone,Rashmi Ravichandran,Cassandra Ogohara,Lauren Carter,Sasha W Tilles,Rino Rappuoli,Sarah R. Leist,David R. Martinez,Matthew Clark,Roland Tisch,Derek T. O'Hagan,Robbert van der Most,Wesley C. Van Voorhis,Davide Corti,Jason S. McLellan,Harry Kleanthous,Timothy P. Sheahan,Kelly D. Smith,Deborah H. Fuller,Francois Villinger,Jesse D. Bloom,Jesse D. Bloom,Bali Pulendran,Ralph S. Baric,Neil P. King,David Veesler +51 more
TL;DR: In this paper, a clinical stage multivalent SARS-CoV-2 spike receptor-binding domain nanoparticle (RBD-NP) vaccine was used to protect mice from SARS CoV 2 challenge after a single immunization.
Journal ArticleDOI
Particulate matter and SARS-CoV-2: A possible model of COVID-19 transmission
Nguyen Thanh Tung,Nguyen Thanh Tung,Po Ching Cheng,Kai Hsien Chi,Ta Chi Hsiao,Timothy Peter Jones,Kelly Ann Berube,Kin Fai Ho,Hsiao Chi Chuang +8 more
TL;DR: It is proposed that PM plays a direct role as a “carrier” of SARS-CoV-2, a highly infectious novel coronavirus that can affect people of all ages in heavily polluted regions and can be explained by upregulation of ACE2 caused by PM.
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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