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
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In vitro screening of a FDA approved chemical library reveals potential inhibitors of SARS-CoV-2 replication
Franck Touret,Magali Gilles,Karine Barral,Antoine Nougairède,Etienne Decroly,Xavier de Lamballerie,Bruno Coutard +6 more
TL;DR: This study screened the Prestwick Chemical Library composed of 1,520 approved drugs in an infected cell-based assay and provided new information on molecules inhibiting SARS-CoV-2 replication in vitro, which could contribute to the short-term repurposing of drugs against Covid-19.
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V367F Mutation in SARS-CoV-2 Spike RBD Emerging during the Early Transmission Phase Enhances Viral Infectivity through Increased Human ACE2 Receptor Binding Affinity.
Junxian Ou,Zhonghua Zhou,Ruixue Dai,Jing Zhang,Shan Zhao,Xiaowei Wu,Wendong Lan,Yi Ren,Lilian Cui,Qiaoshuai Lan,Lu Lu,Donald Seto,James Chodosh,Jianguo Wu,Gong Zhang,Qiwei Zhang,Qiwei Zhang +16 more
TL;DR: In this paper, the binding dynamics between SARS-CoV-2 RBD mutants and the human angiotensin-converting enzyme 2 (ACE2) receptor were analyzed in silico.
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SARS-CoV-2 Requires Cholesterol for Viral Entry and Pathological Syncytia Formation
David W. Sanders,Chanelle C. Jumper,Paul J Ackerman,Dan Bracha,Anita Donlic,Hahn Kim,Devin Kenney,Ivan Castello-Serrano,Saori Suzuki,Tomokazu Tamura,Alexander H Tavares,Mohsan Saeed,Alex S. Holehouse,Alexander Ploss,Ilya Levental,Florian Douam,Robert F. Padera,Bruce D. Levy,Clifford P. Brangwynne,Clifford P. Brangwynne +19 more
TL;DR: It is reported that co-culture of human cells expressing the receptor ACE2 with cells expressing SARS-CoV-2 spike, results in synapse-like intercellular contacts that initiate cell-cell fusion, producing syncytia resembling those identified in lungs of COVID-19 patients.
Journal ArticleDOI
A comprehensive investigation of the mRNA and protein level of ACE2, the putative receptor of SARS-CoV-2, in human tissues and blood cells.
Yiliang Wang,Yun Wang,Weisheng Luo,Lianzhou Huang,Ji Xiao,Feng Li,Shurong Qin,Xiaowei Song,Yanting Wu,Qiongzhen Zeng,Fujun Jin,Wang Yifei +11 more
TL;DR: It is suggested that ACE2 protein is mainly expressed in the small intestine, kidney, gallbladder, and testis, while the abundance of which in brain-associated tissues and blood common cells is low, which may indicate the risk of different human organs vulnerable to SARS-CoV-2 infection.
Journal ArticleDOI
Imprinted antibody responses against SARS-CoV-2 Omicron sublineages
Young-Jun Park,Dora Pinto,Alexandra C. Walls,Zhuoming Li,Anna De Marco,Fabio Benigni,Fabrizia Zatta,Chiara Silacci-Fregni,Jessica Bassi,Kaitlin R. Sprouse,Amin Addetia,John E. Bowen,Cameron Stewart,Martina Giurdanella,Christian Saliba,Barbara Guarino,Michael Schmid,Nicholas Franko,Jennifer Logue,Ha V. Dang,Kevin Hauser,J. Di Iulio,William A. Rivera,Gretja Schnell,Anushka Rajesh,Jiayi Zhou,Nisar A. Farhat,Hannah Kaiser,Martin Montiel-Ruiz,Julia Noack,Florian A. Lempp,Javier Janer,Rana Abdelnabi,Piet Maes,Paolo Ferrari,Alessandro Ceschi,Olivier Giannini,G. D. de Melo,Lauriane Kergoat,Hervé Bourhy,Johan Neyts,Leah Soriaga,Lisa A. Purcell,Gyorgy Snell,Sean P. J. Whelan,Antonio Lanzavecchia,Herbert W. Virgin,Luca Piccoli,Helen Y. Chu,Matteo Samuele Pizzuto,Davide Corti,David Veesler +51 more
TL;DR: It is shown that hybrid immunity or vaccine boosters result in potent plasma neutralizing activity against Omicron BA.1 and BA.2 and that breakthrough infections, but not vaccination-only, induceneutralizing activity in the nasal mucosa.
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