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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In vivo structural characterization of the SARS-CoV-2 RNA genome identifies host proteins vulnerable to repurposed drugs.
Lei Sun,Pan Li,Xiaohui Ju,Jian Rao,Wenze Huang,Lili Ren,Shaojun Zhang,Tuanlin Xiong,Kui Xu,Xiaolin Zhou,Mingli Gong,Eric A. Miska,Eric A. Miska,Qiang Ding,Jianwei Wang,Qiangfeng Cliff Zhang +15 more
TL;DR: In this article, the structural landscape of SARS-CoV-2 RNA in infected human cells and from refolded RNAs, as well as the regulatory untranslated regions of six other coronaviruses were determined using icSHAPE.
Journal ArticleDOI
COVID-19-associated cardiovascular morbidity in older adults: a position paper from the Italian Society of Cardiovascular Researches.
Francesco Moccia,Andrea Gerbino,Vincenzo Lionetti,Michele Miragoli,Luca Munaron,Pasquale Pagliaro,Teresa Pasqua,Claudia Penna,Carmine Rocca,Michele Samaja,Tommaso Angelone +10 more
TL;DR: This position paper hypothesizes and discusses more suggestive cellular and molecular mechanisms whereby SARS-CoV-2 may lead to detrimental consequences to the cardiovascular system, and focuses on aging, cytokine storm, NLRP3/inflammasome, hypoxemia, and air pollution.
Journal ArticleDOI
Peptide and peptide-based inhibitors of SARS-CoV-2 entry.
Desiree Schütz,Yasser B. Ruiz-Blanco,Jan Münch,Frank Kirchhoff,Elsa Sanchez-Garcia,Janis A. Müller +5 more
TL;DR: The current status of peptides inhibiting SARS-CoV-2 entry is summarized and the strategies used to design peptides targeting the ACE2 receptor or the viral Spike protein and its activating proteases furin, transmembrane serine protease 2 (TMPRSS2), or cathepsin L.
Journal ArticleDOI
SARS-CoV-2 genomic surveillance in Taiwan revealed novel ORF8-deletion mutant and clade possibly associated with infections in Middle East.
Yu-Nong Gong,Yu-Nong Gong,Kuo Chien Tsao,Kuo Chien Tsao,Mei Jen Hsiao,Chung Guei Huang,Chung Guei Huang,Peng Nien Huang,Peng Nien Huang,Po Wei Huang,Kuo-Ming Lee,Yi-Chun Liu,Shu Li Yang,Shu Li Yang,Rei-Lin Kuo,Kuan-Fu Chen,Kuan-Fu Chen,Yen Chin Liu,Sheng-Yu Huang,Hsing-I Huang,Ming Tsan Liu,Ji Rong Yang,Cheng-Hsun Chiu,Cheng-Ta Yang,Cheng-Ta Yang,Guang-Wu Chen,Guang-Wu Chen,Shin-Ru Shih +27 more
TL;DR: Investigating the genomic variation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Taiwan revealed a new ORF8-deletion mutant and a virus clade that may be associated with infections in the Middle East, which contributed to a better understanding of the global SARS- covirus 2 transmission dynamics.
Journal ArticleDOI
Aptamer Blocking Strategy Inhibits SARS-CoV-2 Virus Infection.
Miao Sun,Siwen Liu,Xinyu Wei,Shuang Wan,Mengjiao Huang,Ting Song,Yao Lu,Xiaonan Weng,Zhu Lin,Honglin Chen,Yanling Song,Chaoyong Yang,Chaoyong Yang +12 more
TL;DR: In this paper, an aptamer blocking strategy was proposed by engineering aptamers' binding to the region on SRBD that directly mediates ACE2 receptor engagement, leading to block SARS-CoV-2 infection.
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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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