Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor.
Jun Lan,Jiwan Ge,Jinfang Yu,Sisi Shan,Huan Zhou,Shilong Fan,Qi Zhang,Xuanling Shi,Qisheng Wang,Linqi Zhang,Xinquan Wang +10 more
TLDR
High-resolution crystal structures of the receptor-binding domain of the spike protein of SARS-CoV-2 and SARS -CoV in complex with ACE2 provide insights into the binding mode of these coronaviruses and highlight essential ACE2-interacting residues.Abstract:
A new and highly pathogenic coronavirus (severe acute respiratory syndrome coronavirus-2, SARS-CoV-2) caused an outbreak in Wuhan city, Hubei province, China, starting from December 2019 that quickly spread nationwide and to other countries around the world1–3. Here, to better understand the initial step of infection at an atomic level, we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 bound to the cell receptor ACE2. The overall ACE2-binding mode of the SARS-CoV-2 RBD is nearly identical to that of the SARS-CoV RBD, which also uses ACE2 as the cell receptor4. Structural analysis identified residues in the SARS-CoV-2 RBD that are essential for ACE2 binding, the majority of which either are highly conserved or share similar side chain properties with those in the SARS-CoV RBD. Such similarity in structure and sequence strongly indicate convergent evolution between the SARS-CoV-2 and SARS-CoV RBDs for improved binding to ACE2, although SARS-CoV-2 does not cluster within SARS and SARS-related coronaviruses1–3,5. The epitopes of two SARS-CoV antibodies that target the RBD are also analysed for binding to the SARS-CoV-2 RBD, providing insights into the future identification of cross-reactive antibodies. High-resolution crystal structures of the receptor-binding domain of the spike protein of SARS-CoV-2 and SARS-CoV in complex with ACE2 provide insights into the binding mode of these coronaviruses and highlight essential ACE2-interacting residues.read more
Citations
More filters
Journal ArticleDOI
Structural basis of receptor recognition by SARS-CoV-2.
Jian Shang,Gang Ye,Ke Shi,Yushun Wan,Chuming Luo,Hideki Aihara,Qibin Geng,Ashley Auerbach,Fang Li +8 more
TL;DR: This study determines the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 (engineered to facilitate crystallization) in complex with ACE2 and sheds light on the structural features that increase its binding affinity to ACE2.
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
SARS-CoV-2 variants, spike mutations and immune escape.
William T. Harvey,Alessandro M Carabelli,Ben Jackson,Ravindra K. Gupta,E. Thomson,E. Thomson,Ewan M. Harrison,Ewan M. Harrison,Catherine Ludden,Richard Reeve,Andrew Rambaut,Sharon J. Peacock,David Robertson +12 more
TL;DR: A review of the literature on mutations of the SARS-CoV-2 spike protein, the primary antigen, focusing on their impacts on antigenicity and contextualizing them in the protein structure is presented in this article.
Journal ArticleDOI
Coronavirus biology and replication: implications for SARS-CoV-2.
TL;DR: The first discoveries that shape the current understanding of SARS-CoV-2 infection throughout the intracellular viral life cycle are summarized and relate that to the knowledge of coronavirus biology.
Journal ArticleDOI
Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody.
Dora Pinto,Young-Jun Park,Martina Beltramello,Alexandra C. Walls,M. Alejandra Tortorici,M. Alejandra Tortorici,Siro Bianchi,Stefano Jaconi,Katja Culap,Fabrizia Zatta,Anna De Marco,Alessia Peter,Barbara Guarino,Roberto Spreafico,Elisabetta Cameroni,James Brett Case,Rita E. Chen,Colin Havenar-Daughton,Gyorgy Snell,Amalio Telenti,Herbert W. Virgin,Antonio Lanzavecchia,Michael S. Diamond,Katja Fink,David Veesler,Davide Corti +25 more
TL;DR: Several monoclonal antibodies that target the S glycoprotein of SARS-CoV-2, which was identified from memory B cells of an individual who was infected with severe acute respiratory syndrome coronavirus (SARS- coV) in 2003, and one antibody (named S309) potently neutralization, which may limit the emergence of neutralization-escape mutants.
References
More filters
Journal ArticleDOI
Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China.
Dawei Wang,Bo Hu,Chang Hu,Fangfang Zhu,Xing Liu,Jing Zhang,Binbin Wang,Hui Xiang,Zhenshun Cheng,Yong Xiong,Yan Zhao,Yirong Li,Xinghuan Wang,Zhiyong Peng +13 more
TL;DR: The epidemiological and clinical characteristics of novel coronavirus (2019-nCoV)-infected pneumonia in Wuhan, China, and hospital-associated transmission as the presumed mechanism of infection for affected health professionals and hospitalized patients are described.
Journal ArticleDOI
SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor
Markus Hoffmann,Hannah Kleine-Weber,Simon Schroeder,Nadine Krüger,Tanja Herrler,Sandra Erichsen,Tobias S. Schiergens,Georg Herrler,Nai Huei Wu,Andreas Nitsche,Marcel A. Müller,Christian Drosten,Christian Drosten,Stefan Pöhlmann +13 more
TL;DR: It is demonstrated that SARS-CoV-2 uses the SARS -CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming, and it is shown that the sera from convalescent SARS patients cross-neutralized Sars-2-S-driven entry.
Journal ArticleDOI
Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding.
Roujian Lu,Xiang Zhao,Juan Li,Peihua Niu,Bo Yang,Honglong Wu,Wenling Wang,Hao Song,Baoying Huang,Na Zhu,Yuhai Bi,Xuejun Ma,Faxian Zhan,Liang Wang,Tao Hu,Hong Zhou,Zhenhong Hu,Weimin Zhou,Li Zhao,Jing Chen,Yao Meng,Ji Wang,Yang Lin,Jianying Yuan,Zhihao Xie,Jinmin Ma,William J. Liu,Dayan Wang,Wenbo Xu,Edward C. Holmes,George F. Gao,George F. Gao,Guizhen Wu,Weijun Chen,Weifeng Shi,Wenjie Tan,Wenjie Tan +36 more
TL;DR: The phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans.
Journal ArticleDOI
A new coronavirus associated with human respiratory disease in China.
Fan Wu,Su Zhao,Bin Yu,Yan-Mei Chen,Wen Wang,Zhi gang Song,Yi Hu,Zhao Wu Tao,Jun Hua Tian,Yuan Yuan Pei,Ming Li Yuan,Yu Ling Zhang,Fa Hui Dai,Yi Liu,Qi Min Wang,Jiao Jiao Zheng,Lin Xu,Edward C. Holmes,Edward C. Holmes,Yong-Zhen Zhang,Yong-Zhen Zhang +20 more
TL;DR: Phylogenetic and metagenomic analyses of the complete viral genome of a new coronavirus from the family Coronaviridae reveal that the virus is closely related to a group of SARS-like coronaviruses found in bats in China.
Journal ArticleDOI
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
TL;DR: 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.
Related Papers (5)
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