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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A multi-pronged approach targeting SARS-CoV-2 proteins using ultra-large virtual screening.
Christoph Gorgulla,Krishna Mohan Padmanabha Das,Kendra E. Leigh,Marco Cespugli,Patrick D. Fischer,Patrick D. Fischer,Zi-Fu Wang,Guilhem Tesseyre,Shreya Pandita,Alec Shnapir,Anthony Calderaio,Minko Gechev,Alexander Rose,Noam Lewis,Colin Hutcheson,Erez Yaffe,Roni Luxenburg,Henry D. Herce,Vedat Durmaz,Thanos D. Halazonetis,Konstantin Fackeldey,Konstantin Fackeldey,J. J. Patten,Alexander Chuprina,Igor Dziuba,Alla Plekhova,Yurii S. Moroz,Dmytro S. Radchenko,Olga Tarkhanova,Irina Yavnyuk,Christian Gruber,Ryan Yust,Dave Payne,Anders M. Näär,Mark N. Namchuk,Robert A. Davey,Gerhard Wagner,Jamie Kinney,Haribabu Arthanari +38 more
TL;DR: In this article, a structure-based virtual campaign was proposed to search for inhibitors that target SARS-CoV-2, where roughly 1 billion molecules against each of 40 different target sites on 17 different potential viral and host targets.
Journal ArticleDOI
Structural Analysis of Neutralizing Epitopes of the SARS-CoV-2 Spike to Guide Therapy and Vaccine Design Strategies.
Maxwell T. Finkelstein,Adam G. Mermelstein,Emma Parker Miller,Paul C. Seth,Erik-Stephane D. Stancofski,Daniela Fera +5 more
TL;DR: In this paper, the authors highlight recent studies that provide atomic-resolution structural details important for the development of monoclonal antibodies (mAbs) that can be used therapeutically and prophylactically and for vaccines against SARS-CoV-2.
Journal ArticleDOI
Short linear motif candidates in the cell entry system used by SARS-CoV-2 and their potential therapeutic implications.
Bálint Mészáros,Hugo Sámano-Sánchez,Jesús Alvarado-Valverde,Jelena Čalyševa,Elizabeth Martínez-Pérez,Renato J. Alves,Denis C. Shields,Manjeet Kumar,Friedrich Rippmann,Lucía B. Chemes,Toby J. Gibson +10 more
TL;DR: In this article, the authors examined the sequences of ACE2 and integrins with the Eukaryotic Linear Motif (ELM) resource and identified candidate short linear motifs (SLiMs) in their short, unstructured, cytosolic tails with potential roles in endocytosis, membrane dynamics, autophagy, and cell signaling.
Journal ArticleDOI
Sexual dimorphism in COVID-19: potential clinical and public health implications
TL;DR: Zhou et al. as mentioned in this paper discussed how sex hormones, comorbidities, and the sex chromosome complement influence these mechanisms in the context of COVID-19 and suggested that sex differences could be considered in future pandemic surveillance and treatment of patients with COVID19 to help to achieve better disease stratification and improved outcomes.
Journal ArticleDOI
Kobophenol A Inhibits Binding of Host ACE2 Receptor with Spike RBD Domain of SARS-CoV-2, a Lead Compound for Blocking COVID-19.
Suresh Gangadevi,Vishnu Nayak Badavath,Abhishek Thakur,Na Yin,Steven De Jonghe,Orlando Acevedo,Dirk Jochmans,Pieter Leyssen,Ke Wang,Johan Neyts,Tao Yujie,Galia Blum +11 more
TL;DR: In this paper, Kobophenol A was found to block the interaction between the ACE2 receptor and S1-RBD in vitro with an IC50 of 181 ± 004 μM and inhibit SARS-CoV-2 viral infection in cells with an EC50 of 716 μM.
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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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