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10.1096/fj.202000654R

http://scihub22266oqcxt.onion/10.1096/fj.202000654R
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32367579!7383733!32367579
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suck abstract from ncbi


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pmid32367579      FASEB+J 2020 ; 34 (6): 7253-7264
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  • The lysosome: A potential juncture between SARS-CoV-2 infectivity and Niemann-Pick disease type C, with therapeutic implications #MMPMID32367579
  • Ballout RA; Sviridov D; Bukrinsky MI; Remaley AT
  • FASEB J 2020[Jun]; 34 (6): 7253-7264 PMID32367579show ga
  • Drug repurposing is potentially the fastest available option in the race to identify safe and efficacious drugs that can be used to prevent and/or treat COVID-19. By describing the life cycle of the newly emergent coronavirus, SARS-CoV-2, in light of emerging data on the therapeutic efficacy of various repurposed antimicrobials undergoing testing against the virus, we highlight in this review a possible mechanistic convergence between some of these tested compounds. Specifically, we propose that the lysosomotropic effects of hydroxychloroquine and several other drugs undergoing testing may be responsible for their demonstrated in vitro antiviral activities against COVID-19. Moreover, we propose that Niemann-Pick disease type C (NPC), a lysosomal storage disorder, may provide new insights into potential future therapeutic targets for SARS-CoV-2, by highlighting key established features of the disorder that together result in an "unfavorable" host cellular environment that may interfere with viral propagation. Our reasoning evolves from previous biochemical and cell biology findings related to NPC, coupled with the rapidly evolving data on COVID-19. Our overall aim is to suggest that pharmacological interventions targeting lysosomal function in general, and those particularly capable of reversibly inducing transient NPC-like cellular and biochemical phenotypes, constitute plausible mechanisms that could be used to therapeutically target COVID-19.
  • |*Drug Repositioning[MESH]
  • |ADAM17 Protein/physiology[MESH]
  • |Adenosine Monophosphate/analogs & derivatives/pharmacology/therapeutic use[MESH]
  • |Alanine/analogs & derivatives/pharmacology/therapeutic use[MESH]
  • |Angiotensin-Converting Enzyme 2[MESH]
  • |Antiviral Agents/*pharmacokinetics/pharmacology/therapeutic use[MESH]
  • |Benzylisoquinolines/pharmacology/therapeutic use[MESH]
  • |Betacoronavirus/*physiology[MESH]
  • |Biological Transport[MESH]
  • |COVID-19[MESH]
  • |COVID-19 Drug Treatment[MESH]
  • |Cathepsin L/physiology[MESH]
  • |Coronavirus Infections/*drug therapy[MESH]
  • |Endocytosis[MESH]
  • |Endosomes/drug effects/physiology/*virology[MESH]
  • |Glycopeptides/pharmacology/therapeutic use[MESH]
  • |Humans[MESH]
  • |Hydroxychloroquine/pharmacokinetics/*pharmacology/therapeutic use[MESH]
  • |Intracellular Signaling Peptides and Proteins/antagonists & inhibitors/deficiency/physiology[MESH]
  • |Lysosomes/drug effects/metabolism/*virology[MESH]
  • |Membrane Lipids/metabolism[MESH]
  • |Membrane Microdomains/physiology[MESH]
  • |Niemann-Pick C1 Protein[MESH]
  • |Niemann-Pick Disease, Type C/metabolism/*pathology[MESH]
  • |Oxysterols/metabolism[MESH]
  • |Pandemics[MESH]
  • |Peptidyl-Dipeptidase A/metabolism[MESH]
  • |Pneumonia, Viral/*drug therapy[MESH]
  • |Receptors, Virus/metabolism[MESH]
  • |SARS-CoV-2[MESH]
  • |Serine Endopeptidases/physiology[MESH]
  • |Triazoles/pharmacology/therapeutic use[MESH]


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