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10.1128/JVI.00127-20

http://scihub22266oqcxt.onion/10.1128/JVI.00127-20
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31996437!7081895!31996437
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suck abstract from ncbi


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pmid31996437      J+Virol 2020 ; 94 (7): ä
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  • Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus #MMPMID31996437
  • Wan Y; Shang J; Graham R; Baric RS; Li F
  • J Virol 2020[Mar]; 94 (7): ä PMID31996437show ga
  • Recently, a novel coronavirus (2019-nCoV) has emerged from Wuhan, China, causing symptoms in humans similar to those caused by severe acute respiratory syndrome coronavirus (SARS-CoV). Since the SARS-CoV outbreak in 2002, extensive structural analyses have revealed key atomic-level interactions between the SARS-CoV spike protein receptor-binding domain (RBD) and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. Here, we analyzed the potential receptor usage by 2019-nCoV, based on the rich knowledge about SARS-CoV and the newly released sequence of 2019-nCoV. First, the sequence of 2019-nCoV RBD, including its receptor-binding motif (RBM) that directly contacts ACE2, is similar to that of SARS-CoV, strongly suggesting that 2019-nCoV uses ACE2 as its receptor. Second, several critical residues in 2019-nCoV RBM (particularly Gln493) provide favorable interactions with human ACE2, consistent with 2019-nCoV's capacity for human cell infection. Third, several other critical residues in 2019-nCoV RBM (particularly Asn501) are compatible with, but not ideal for, binding human ACE2, suggesting that 2019-nCoV has acquired some capacity for human-to-human transmission. Last, while phylogenetic analysis indicates a bat origin of 2019-nCoV, 2019-nCoV also potentially recognizes ACE2 from a diversity of animal species (except mice and rats), implicating these animal species as possible intermediate hosts or animal models for 2019-nCoV infections. These analyses provide insights into the receptor usage, cell entry, host cell infectivity and animal origin of 2019-nCoV and may help epidemic surveillance and preventive measures against 2019-nCoV.IMPORTANCE The recent emergence of Wuhan coronavirus (2019-nCoV) puts the world on alert. 2019-nCoV is reminiscent of the SARS-CoV outbreak in 2002 to 2003. Our decade-long structural studies on the receptor recognition by SARS-CoV have identified key interactions between SARS-CoV spike protein and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. One of the goals of SARS-CoV research was to build an atomic-level iterative framework of virus-receptor interactions to facilitate epidemic surveillance, predict species-specific receptor usage, and identify potential animal hosts and animal models of viruses. Based on the sequence of 2019-nCoV spike protein, we apply this predictive framework to provide novel insights into the receptor usage and likely host range of 2019-nCoV. This study provides a robust test of this reiterative framework, providing the basic, translational, and public health research communities with predictive insights that may help study and battle this novel 2019-nCoV.
  • |Amino Acid Sequence[MESH]
  • |Angiotensin-Converting Enzyme 2[MESH]
  • |Animals[MESH]
  • |Betacoronavirus/classification/*physiology[MESH]
  • |COVID-19[MESH]
  • |China[MESH]
  • |Chiroptera/virology[MESH]
  • |Coronavirus Infections/*virology[MESH]
  • |Host Specificity[MESH]
  • |Humans[MESH]
  • |Models, Molecular[MESH]
  • |Peptidyl-Dipeptidase A/*chemistry[MESH]
  • |Phylogeny[MESH]
  • |Pneumonia, Viral/*virology[MESH]
  • |Protein Domains[MESH]
  • |Receptors, Virus/*chemistry[MESH]
  • |SARS-CoV-2[MESH]
  • |Sequence Alignment[MESH]
  • |Severe acute respiratory syndrome-related coronavirus/physiology[MESH]


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