Structural basis of receptor recognition by SARS-CoV-2.
Jian Shang,Gang Ye,Ke Shi,Yushun Wan,Chuming Luo,Hideki Aihara,Qibin Geng,Ashley Auerbach,Fang Li +8 more
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TLDR
This study determines the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 (engineered to facilitate crystallization) in complex with ACE2 and sheds light on the structural features that increase its binding affinity to ACE2.Abstract:
A novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) recently emerged and is rapidly spreading in humans, causing COVID-191,2. A key to tackling this pandemic is to understand the receptor recognition mechanism of the virus, which regulates its infectivity, pathogenesis and host range. SARS-CoV-2 and SARS-CoV recognize the same receptor—angiotensin-converting enzyme 2 (ACE2)—in humans3,4. Here we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 (engineered to facilitate crystallization) in complex with ACE2. In comparison with the SARS-CoV RBD, an ACE2-binding ridge in SARS-CoV-2 RBD has a more compact conformation; moreover, several residue changes in the SARS-CoV-2 RBD stabilize two virus-binding hotspots at the RBD–ACE2 interface. These structural features of SARS-CoV-2 RBD increase its ACE2-binding affinity. Additionally, we show that RaTG13, a bat coronavirus that is closely related to SARS-CoV-2, also uses human ACE2 as its receptor. The differences among SARS-CoV-2, SARS-CoV and RaTG13 in ACE2 recognition shed light on the potential animal-to-human transmission of SARS-CoV-2. This study provides guidance for intervention strategies that target receptor recognition by SARS-CoV-2. The crystal structure of the receptor-binding domain of the SARS-CoV-2 spike in complex with human ACE2, compared with the receptor-binding domain of SARS-CoV, sheds light on the structural features that increase its binding affinity to ACE2.read more
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The trinity of COVID-19: immunity, inflammation and intervention.
Matthew Zirui Tay,Chek Meng Poh,Laurent Rénia,Laurent Rénia,Paul A. MacAry,Lisa F. P. Ng,Lisa F. P. Ng,Lisa F. P. Ng +7 more
TL;DR: The interaction of SARS-CoV-2 with the immune system and the subsequent contribution of dysfunctional immune responses to disease progression is described and the implications of these approaches for potential therapeutic interventions that target viral infection and/or immunoregulation are highlighted.
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Characteristics of SARS-CoV-2 and COVID-19
TL;DR: The basic virology of SARS-CoV-2 is described, including genomic characteristics and receptor use, highlighting its key difference from previously known coronaviruses.
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Cell entry mechanisms of SARS-CoV-2.
TL;DR: Key cell entry mechanisms of SARS-CoV-2 that potentially contribute to the immune evasion, cell infectivity, and wide spread of the virus are identified using biochemical and pseudovirus entry assays and the potency and evasiveness are highlighted.
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Post-acute COVID-19 syndrome.
Ani Nalbandian,Kartik Sehgal,Kartik Sehgal,Aakriti Gupta,Aakriti Gupta,Mahesh V. Madhavan,Claire McGroder,Jacob S. Stevens,Joshua R. Cook,Anna S. Nordvig,Daniel Shalev,Tejasav S. Sehrawat,Neha Ahluwalia,Behnood Bikdeli,Donald Dietz,Caroline Der-Nigoghossian,Nadia Liyanage-Don,Gregg F. Rosner,Elana J. Bernstein,Sumit Mohan,Akinpelumi A Beckley,David S. Seres,Toni K. Choueiri,Toni K. Choueiri,Nir Uriel,John C. Ausiello,Domenico Accili,Daniel E. Freedberg,Matthew R. Baldwin,Allan Schwartz,Daniel Brodie,Christine Kim Garcia,Mitchell S.V. Elkind,Jean M. Connors,Jean M. Connors,John P. Bilezikian,Donald W. Landry,Elaine Wan +37 more
TL;DR: A comprehensive review of the current literature on post-acute COVID-19, its pathophysiology and its organ-specific sequelae is provided in this paper, where the authors discuss relevant considerations for the multidisciplinary care of COPD survivors and propose a framework for the identification of those at high risk for COPD and their coordinated management through dedicated COPD clinics.
Journal ArticleDOI
Extrapulmonary manifestations of COVID-19.
Aakriti Gupta,Aakriti Gupta,Mahesh V. Madhavan,Kartik Sehgal,Kartik Sehgal,Nandini Nair,Shiwani Mahajan,Tejasav S. Sehrawat,Behnood Bikdeli,Behnood Bikdeli,Neha Ahluwalia,John C. Ausiello,Elaine Wan,Daniel E. Freedberg,Ajay J. Kirtane,Sahil A. Parikh,Mathew S. Maurer,Anna S. Nordvig,Domenico Accili,Joan M. Bathon,Sumit Mohan,Kenneth A. Bauer,Kenneth A. Bauer,Martin B. Leon,Harlan M. Krumholz,Nir Uriel,Mandeep R. Mehra,Mitchell S.V. Elkind,Mitchell S.V. Elkind,Gregg W. Stone,Allan Schwartz,David D. Ho,John P. Bilezikian,Donald W. Landry +33 more
TL;DR: The extrapulmonary organ-specific pathophysiology, presentations and management considerations for patients with COVID-19 are reviewed to aid clinicians and scientists in recognizing and monitoring the spectrum of manifestations, and in developing research priorities and therapeutic strategies for all organ systems involved.
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SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor
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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.
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