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10.1038/s41467-021-21213-4

http://scihub22266oqcxt.onion/10.1038/s41467-021-21213-4
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33574281!7878750!33574281
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suck abstract from ncbi


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pmid33574281      Nat+Commun 2021 ; 12 (1): 961
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  • A genome-wide CRISPR screen identifies host factors that regulate SARS-CoV-2 entry #MMPMID33574281
  • Zhu Y; Feng F; Hu G; Wang Y; Yu Y; Zhu Y; Xu W; Cai X; Sun Z; Han W; Ye R; Qu D; Ding Q; Huang X; Chen H; Xu W; Xie Y; Cai Q; Yuan Z; Zhang R
  • Nat Commun 2021[Feb]; 12 (1): 961 PMID33574281show ga
  • The global spread of SARS-CoV-2 is posing major public health challenges. One feature of SARS-CoV-2 spike protein is the insertion of multi-basic residues at the S1/S2 subunit cleavage site. Here, we find that the virus with intact spike (Sfull) preferentially enters cells via fusion at the plasma membrane, whereas a clone (Sdel) with deletion disrupting the multi-basic S1/S2 site utilizes an endosomal entry pathway. Using Sdel as model, we perform a genome-wide CRISPR screen and identify several endosomal entry-specific regulators. Experimental validation of hits from the CRISPR screen shows that host factors regulating the surface expression of angiotensin-converting enzyme 2 (ACE2) affect entry of Sfull virus. Animal-to-animal transmission with the Sdel virus is reduced compared to Sfull in the hamster model. These findings highlight the critical role of the S1/S2 boundary of SARS-CoV-2 spike protein in modulating virus entry and transmission and provide insights into entry of coronaviruses.
  • |*CRISPR-Cas Systems[MESH]
  • |*Genome-Wide Association Study[MESH]
  • |*Host-Pathogen Interactions[MESH]
  • |*Virus Internalization[MESH]
  • |A549 Cells[MESH]
  • |Angiotensin-Converting Enzyme 2/genetics/metabolism[MESH]
  • |Animals[MESH]
  • |COVID-19/genetics/*virology[MESH]
  • |Chlorocebus aethiops[MESH]
  • |Disease Models, Animal[MESH]
  • |Endosomes/virology[MESH]
  • |HeLa Cells[MESH]
  • |Humans[MESH]
  • |Mesocricetus[MESH]
  • |SARS-CoV-2/*physiology[MESH]
  • |Serine Endopeptidases[MESH]
  • |Spike Glycoprotein, Coronavirus/metabolism[MESH]


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  • suck abstract from ncbi

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