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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The antigenic anatomy of SARS-CoV-2 receptor binding domain.
Wanwisa Dejnirattisai,D. Zhou,Helen M. Ginn,Helen M. E. Duyvesteyn,Piyada Supasa,James Brett Case,Yuguang Zhao,Thomas S. Walter,Alexander J. Mentzer,Chang Liu,Beibei Wang,Guido C. Paesen,J Slon-Campos,Cesar Lopez-Camacho,Natasha M. Kafai,Adam L. Bailey,Rita E. Chen,Baoling Ying,Craig Thompson,Jai S Bolton,Alex Fyfe,Sunetra Gupta,Tiong Kit Tan,Javier Gilbert-Jaramillo,William James,Michael L. Knight,Miles W. Carroll,Donal T. Skelly,Christina Dold,Yanchun Peng,R Levin,Tao Dong,Andrew J. Pollard,Julian C. Knight,Paul Klenerman,Nigel J. Temperton,David R. Hall,Mark A. Williams,Neil G. Paterson,Felicity K.R. Bertram,C. Alistair Siebert,Daniel K. Clare,Andy G. Howe,Julika Radecke,Yun Song,Alain Townsend,Kuan-Ying A. Huang,Elizabeth E. Fry,Juthathip Mongkolsapaya,Juthathip Mongkolsapaya,Michael S. Diamond,Jingshan Ren,David I. Stuart,Gavin R. Screaton +53 more
TL;DR: In this paper, the authors identify 377 human monoclonal antibodies (mAbs) recognizing the virus spike and focus mainly on 80 that bind the receptor binding domain (RBD) and devise a competition data-driven method to map RBD binding sites.
Journal ArticleDOI
COVID-19, diabetes mellitus and ACE2: The conundrum.
Rimesh Pal,Anil Bhansali +1 more
TL;DR: The role of angiotensin-converting enzyme 2 (ACE2) in the association between diabetes mellitus (DM) and COVID-19 is plausible and it can be assumed that patients with DM are more likely to be older than those without DM and advancing age has consis-tently been shown to be associated with poor prognosis inCO VID-19.
Journal ArticleDOI
The role of furin cleavage site in SARS-CoV-2 spike protein-mediated membrane fusion in the presence or absence of trypsin.
Shuai Xia,Qiaoshuai Lan,Shan Su,Xinling Wang,Wei Xu,Zezhong Liu,Yun Zhu,Qian Wang,Lu Lu,Shibo Jiang +9 more
TL;DR: It has been speculated that RRAR, a unique furin-like cleavage site in the spike protein (S), which is absent in other lineage B βCoVs, such as SARS-CoV, is responsible for its high infectivity and transmissibility.
Journal ArticleDOI
Nanotechnology for COVID-19: Therapeutics and Vaccine Research.
Gaurav Chauhan,Marc J. Madou,Marc J. Madou,Sourav Kalra,Vianni Chopra,Deepa Ghosh,Sergio O. Martinez-Chapa +6 more
TL;DR: Recent as well as ongoing nanotechnology-based therapeutic and prophylactic strategies to fight against this pandemic are discussed, outlining the key areas for nanoscientists to step in.
Journal ArticleDOI
COVID-19 Coronavirus Vaccine Design Using Reverse Vaccinology and Machine Learning.
TL;DR: It is proposed that an “Sp/Nsp cocktail vaccine” containing a structural protein (Sp) and a non-structural protein(s) (Nsp) would stimulate effective complementary immune responses and have the potential for effective and safe COVID-19 vaccine development.
References
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Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China
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Eric F. Pettersen,Thomas D. Goddard,Conrad C. Huang,Gregory S. Couch,Daniel M. Greenblatt,Elaine C. Meng,Thomas E. Ferrin +6 more
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Journal ArticleDOI
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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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