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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The SARS-CoV-2 Spike variant D614G favors an open conformational state.
Rachael A. Mansbach,Srirupa Chakraborty,Kien Nguyen,David C. Montefiori,Bette T. Korber,Sandrasegaram Gnanakaran +5 more
TL;DR: In this article, the authors show that changes in the protein energetics favor a higher population of infection-capable states in the G-form through release of asymmetry present in the D-form inter-protomer interactions.
Journal ArticleDOI
Making waves: Wastewater surveillance of SARS-CoV-2 for population-based health management.
Janelle R. Thompson,Yarlagadda V. Nancharaiah,Xiaoqiong Gu,Wei Lin Lee,Verónica Beatriz Rajal,Monamie Bhadra Haines,Rosina Girones,Lee Ching Ng,Eric J. Alm,Stefan Wuertz +9 more
TL;DR: In this article, the authors proposed an aggregate wastewater-monitoring system at the level of a wastewater treatment plant and exploratory or confirmatory monitoring of the sewerage system at neighborhood scale to identify or confirm clusters of infection or assess impact of control measures where transmission has been established.
Journal ArticleDOI
SARS-CoV-2 Cell Entry Factors ACE2 and TMPRSS2 Are Expressed in the Microvasculature and Ducts of Human Pancreas but Are Not Enriched in β Cells
Katie C. Coate,Jeeyeon Cha,Shristi Shrestha,Wenliang Wang,Luciana Mateus Gonçalves,Joana Almaça,Meghan E. Kapp,Maria Fasolino,Ashleigh Morgan,Chunhua Dai,Diane C. Saunders,Rita Bottino,Radhika Aramandla,Regina Jenkins,Roland Stein,Klaus H. Kaestner,Golnaz Vahedi,Marcela Brissova,Alvin C. Powers,Alvin C. Powers +19 more
TL;DR: Findings reduce the likelihood that SARS-CoV-2 directly infects β cells in vivo through ACE2 and TMPRSS2 through co-expression of its canonical cell entry factors, angiotensin converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPR SS2).
Journal ArticleDOI
Coinfection with influenza A virus enhances SARS-CoV-2 infectivity.
Lei Bai,Yongliang Zhao,Jiazhen Dong,Simeng Liang,Ming Guo,Xinjin Liu,Xin Wang,Zhixiang Huang,Xiaoyi Sun,Zhen Zhang,Lianghui Dong,Qianyun Liu,Yucheng Zheng,Danping Niu,Min Xiang,Kun Song,Jiajie Ye,Wenchao Zheng,Zhidong Tang,Mingliang Tang,Yu Zhou,Chao Shen,Ming Dai,Li Zhou,Yu Chen,Huan Yan,Ke Lan,Ke Xu +27 more
TL;DR: In this paper, the authors found that IAV preinfection significantly promoted the infectivity of SARS-CoV-2 in a broad range of cell types, and in vivo, increased infection load and more severe lung damage were observed in mice coinfected with IAV.
Journal ArticleDOI
Real-Time Conformational Dynamics of SARS-CoV-2 Spikes on Virus Particles.
Maolin Lu,Pradeep D. Uchil,Wenwei Li,Desheng Zheng,Daniel S. Terry,Jason Gorman,Wei Shi,Baoshan Zhang,Tongqing Zhou,Shilei Ding,Romain Gasser,Jérémie Prévost,Guillaume Beaudoin-Bussières,Sai Priya Anand,Sai Priya Anand,Annemarie Laumaea,Jonathan R. Grover,Lihong Liu,David D. Ho,John R. Mascola,Andrés Finzi,Andrés Finzi,Peter D. Kwong,Scott C. Blanchard,Walther Mothes +24 more
TL;DR: Conformational preferences observed upon expsoure to convalescent plasma or antibodies suggest mechanisms of neutralization involving either competition with hACE2 for binding to the receptor-binding domain (RBD) or allosteric interference with conformational changes required for entry.
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