Distinct conformational states of SARS-CoV-2 spike protein
Yongfei Cai,Yongfei Cai,Jun Zhang,Jun Zhang,Tianshu Xiao,Tianshu Xiao,Hanqin Peng,Sarah M. Sterling,Richard M. Walsh,Shaun Rawson,Sophia Rits-Volloch,Bing Chen,Bing Chen +12 more
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TLDR
Two cryo–electron microscopy structures derived from a preparation of the full-length S protein, representing its prefusion and postfusion conformations, are reported, advancing the understanding of SARS-CoV-2 entry and may guide the development of vaccines and therapeutics.Abstract:
Intervention strategies are urgently needed to control the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The trimeric viral spike (S) protein catalyzes fusion between viral and target cell membranes to initiate infection. Here, we report two cryo-electron microscopy structures derived from a preparation of the full-length S protein, representing its prefusion (2.9-angstrom resolution) and postfusion (3.0-angstrom resolution) conformations, respectively. The spontaneous transition to the postfusion state is independent of target cells. The prefusion trimer has three receptor-binding domains clamped down by a segment adjacent to the fusion peptide. The postfusion structure is strategically decorated by N-linked glycans, suggesting possible protective roles against host immune responses and harsh external conditions. These findings advance our understanding of SARS-CoV-2 entry and may guide the development of vaccines and therapeutics.read more
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Antibody-mediated cell entry of SARS-CoV-2
M. G. Kibria,Christy L. Lavine,Weichun Tang,Shaowei Wang,H. Gao,Wei Shi,Haisun Zhu,Jewel Voyer,Sophia Rits-Volloch,Keerti,Caihong Bi,Hanqin Peng,Duane R. Wesemann,Jianming Lu,Hang Xie,Michael S. Seaman,Bing Chen +16 more
TL;DR: This paper showed that antibody responses against SARS-CoV-2 may expand the viral tropism to otherwise nonpermissive cell types; they have important implications for viral transmission and pathogenesis.
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Human TMPRSS2 non-catalytic ectodomain and SARS-CoV-2 S2' subunit interaction mediated SARS-CoV-2 endocytosis: a model proposal with virtual screening for potential drug molecules to inhibit this interaction
TL;DR: A novel model for integration of SARS-CoV-2 into host cell via endocytosis as a possible alternative to the prevailing direct fusion model is proposed and targeting the interaction between the hNECD of TMPRSS2 and S2' may serve as an attractive therapeutic target.
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Immune and pathophysiologic profiling of antenatal COVID-19 in the GIFT cohort: A Singaporean case-control study.
Yaxi Gu,Jason M. Low,Jenny Tan,Martirosian Ng,Lisa F. P. Ng,Bhuvaneshwari Shunmuganathan,Paul A. MacAry,Zulkifli Amin,Libby H. Y. Lee,Derrick W. Q. Lian,L. Shek,Yue-Qian Zhong,L. Wang +12 more
TL;DR: Antenatal SARS-CoV-2 infection led to high plasma titres of virus-specific antibodies in infants postnatally, however, this was not reflected in milk; milk-borne antibody levels varied widely.
Journal ArticleDOI
Distinct Conformations of SARS-CoV-2 Omicron Spike Protein and Its Interaction with ACE2 and Antibody
TL;DR: In this paper , the structure of the Omicron spike protein was analyzed in the presence and absence of angiotensin-converting enzyme 2 (ACE2) and antibodies.
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Atomistic Simulations and Network-Based Energetic Profiling of Binding and Allostery in the SARS-CoV-2 Spike Omicron BA.1, BA.1.1, BA.2 and BA.3 Subvariant Complexes with the Host Receptor: Revealing Hidden Functional Roles of the Binding Hotspots in Mediating Epistatic Effects and Long-Range Communication with Allosteric Pockets
TL;DR: In this article , the authors performed all-atom MD simulations of the RBD-ACE2 complexes for BA.1, BA.2 and BA.3 Omicron subvariants.
References
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Journal ArticleDOI
UCSF Chimera--a visualization system for exploratory research and analysis.
Eric F. Pettersen,Thomas D. Goddard,Conrad C. Huang,Gregory S. Couch,Daniel M. Greenblatt,Elaine C. Meng,Thomas E. Ferrin +6 more
TL;DR: Two unusual extensions are presented: Multiscale, which adds the ability to visualize large‐scale molecular assemblies such as viral coats, and Collaboratory, which allows researchers to share a Chimera session interactively despite being at separate locales.
Journal ArticleDOI
Features and development of Coot.
TL;DR: Coot is a molecular-graphics program designed to assist in the building of protein and other macromolecular models and the current state of development and available features are presented.
Journal ArticleDOI
A pneumonia outbreak associated with a new coronavirus of probable bat origin
Peng Zhou,Xing-Lou Yang,Xian Guang Wang,Ben Hu,Lei Zhang,Wei Zhang,Hao Rui Si,Yan Zhu,Bei Li,Chao Lin Huang,Hui-Dong Chen,Jing Chen,Yun Luo,Hua Guo,Ren Di Jiang,Meiqin Liu,Ying Chen,Xu Rui Shen,Xi Wang,Xiao Shuang Zheng,Kai Zhao,Quanjiao Chen,Fei Deng,Lin Lin Liu,Bing Yan,Fa Xian Zhan,Yan-Yi Wang,Gengfu Xiao,Zhengli Shi +28 more
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.
Journal ArticleDOI
SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor
Markus Hoffmann,Hannah Kleine-Weber,Simon Schroeder,Nadine Krüger,Tanja Herrler,Sandra Erichsen,Tobias S. Schiergens,Georg Herrler,Nai Huei Wu,Andreas Nitsche,Marcel A. Müller,Christian Drosten,Christian Drosten,Stefan Pöhlmann +13 more
TL;DR: It is demonstrated that SARS-CoV-2 uses the SARS -CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming, and it is shown that the sera from convalescent SARS patients cross-neutralized Sars-2-S-driven entry.
Book ChapterDOI
Phenix - a comprehensive python-based system for macromolecular structure solution
Paul D. Adams,Paul D. Adams,Pavel V. Afonine,Gábor Bunkóczi,Vincent B. Chen,Ian W. Davis,Nathaniel Echols,Jeffrey J. Headd,Li-Wei Hung,Gary J. Kapral,Ralf W. Grosse-Kunstleve,Airlie J. McCoy,Nigel W. Moriarty,Robert D. Oeffner,Randy J. Read,David S. Richardson,Jane S. Richardson,Thomas C. Terwilliger,Peter H. Zwart +18 more
TL;DR: PHENIX has been developed to provide a comprehensive system for macromolecular crystallographic structure solution with an emphasis on the automation of all procedures.
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