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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Engineered ACE2 receptor therapy overcomes mutational escape of SARS-CoV-2.
Yusuke Higuchi,Tatsuya Suzuki,Takao Arimori,Nariko Ikemura,Emiko Mihara,Yuhei Kirita,Eriko Ohgitani,Osam Mazda,Daisuke Motooka,Shota Nakamura,Yusuke Sakai,Yumi Itoh,Fuminori Sugihara,Yoshiharu Matsuura,Satoaki Matoba,Toru Okamoto,Junichi Takagi,Atsushi Hoshino +17 more
TL;DR: In this paper, an engineered human virus receptor, ACE2, by mutagenesis and screening for binding to the receptor binding domain (RBD), achieved sub-nanomolar affinity to RBD.
Journal ArticleDOI
Prospects for mucosal vaccine: shutting the door on SARS-CoV-2.
TL;DR: This article summarizes the approaches to an effective mucosal vaccine formulation which can be a rewarding approach to combat the unprecedented threat posed by this emerging global pandemic.
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Hypercoagulopathy and Adipose Tissue Exacerbated Inflammation May Explain Higher Mortality in COVID-19 Patients With Obesity.
Gabriel Pasquarelli-do-Nascimento,Heloísa Antoniella Braz-de-Melo,Sara Socorro Faria,Igor de Oliveira Santos,Gary P. Kobinger,Kelly Grace Magalhães +5 more
TL;DR: How obesity is related to a pro-inflammatory and metabolic dysregulation, increased SARS-CoV-2 host cell entry in adipose tissue and induction of hypercoagulopathy, leading people with obesity to develop severe forms of COVID-19 and also death is discussed.
Posted ContentDOI
Landscape analysis of escape variants identifies SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization
Zhuoming Liu,VanBlargan La,Louis Marie Bloyet,Paul W. Rothlauf,Paul W. Rothlauf,Rita E. Chen,Stumpf S,Haiyan Zhao,Errico Jm,Elitza S. Theel,Liebeskind Mj,Alford B,Buchser Wj,Ali H. Ellebedy,Fremont Dh,Michael S. Diamond,Whelan Spj +16 more
TL;DR: By comparing the antibody-mediated mutational landscape in S protein with sequence variation in circulating SARS-CoV-2 strains, it is identified single amino acid substitutions that could attenuate neutralizing immune responses in some humans.
Journal ArticleDOI
Control Measures for SARS-CoV-2: A Review on Light-Based Inactivation of Single-Stranded RNA Viruses
TL;DR: The rate of inactivation of ssRNA viruses in liquid was higher than in air, whereas inactivation on solid surfaces varied with the type of surface, and the efficacy of light-based inactivation was reduced by the presence of absorptive materials.
References
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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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