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
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Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding.
Tyler N. Starr,Allison J. Greaney,Allison J. Greaney,Sarah K Hilton,Sarah K Hilton,Daniel Ellis,Katharine H.D. Crawford,Katharine H.D. Crawford,Adam S. Dingens,Mary Jane Navarro,John E. Bowen,M. Alejandra Tortorici,Alexandra C. Walls,Neil P. King,David Veesler,Jesse D. Bloom,Jesse D. Bloom,Jesse D. Bloom +17 more
TL;DR: It is found that a substantial number of mutations to the RBD are well tolerated or even enhance ACE2 binding, including at ACE2 interface residues that vary across SARS-related coronaviruses.
Journal ArticleDOI
Human neutralizing antibodies elicited by SARS-CoV-2 infection.
Bin Ju,Qi Zhang,Jiwan Ge,Ruoke Wang,Jing Sun,Xiangyang Ge,Jiazhen Yu,Sisi Shan,Bing Zhou,Shuo Song,Xian Tang,Jinfang Yu,Jun Lan,Jing Yuan,Haiyan Wang,Juanjuan Zhao,Shuye Zhang,Youchun Wang,Xuanling Shi,Lei Liu,Jincun Zhao,Xinquan Wang,Zheng Zhang,Linqi Zhang +23 more
TL;DR: In a study of antibodies isolated from patients infected with SARS-CoV-2, antibodies that potently neutralized the virus competed with angiotensin-converting enzyme 2 for binding to the receptor-binding domain of the viral spike protein, suggesting that antibodies that disrupt this interaction could be developed to treat Sars-Cov-2 infection.
Journal ArticleDOI
Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19.
TL;DR: Recent research advance in the structure, function and development of antivirus drugs targeting the spike (S) protein of SARS-CoV-2 is highlighted.
Journal ArticleDOI
A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2.
Chi Xiangyang,Renhong Yan,Jun Zhang,Zhang Guanying,Yuanyuan Zhang,Hao Meng,Zhe Zhang,Pengfei Fan,Dong Yunzhu,Yilong Yang,Chen Zhengshan,Yingying Guo,Jinlong Zhang,Yaning Li,Xiaohong Song,Chen Yi,Lu Xia,Ling Fu,Lihua Hou,Junjie Xu,Changming Yu,Jianmin Li,Qiang Zhou,Wei Chen +23 more
TL;DR: The epitope of 4A8 is defined as the N-terminal domain (NTD) of the S protein by determining with cryo–eletron microscopy its structure in complex with the Sprotein, which points to the NTD as a promising target for therapeutic mAbs against COVID-19.
Journal ArticleDOI
A human neutralizing antibody targets the receptor-binding site of SARS-CoV-2.
Rui Shi,Chao Shan,Xiaomin Duan,Zhihai Chen,Peipei Liu,Jin-Wen Song,Tao Song,Tao Song,Xiaoshan Bi,Xiaoshan Bi,Chao Han,Lianao Wu,Lianao Wu,Ge Gao,Xue Hu,Ya-Nan Zhang,Zhou Tong,Weijin Huang,William J. Liu,Guizhen Wu,Bo Zhang,Lan Wang,Jianxun Qi,Hui Feng,Fu-Sheng Wang,Qihui Wang,George F. Gao,Zhiming Yuan,Jinghua Yan +28 more
TL;DR: Two monoclonal antibodies isolated from a patient with COVID-19 are shown to interfere with SARS-CoV-2–receptor binding, and one displays potent action against this virus in vitro and in a rhesus macaque model.
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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.
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