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10.1126/science.abf4058

http://scihub22266oqcxt.onion/10.1126/science.abf4058
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33495306!7963220!33495306
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suck abstract from ncbi


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pmid33495306      Science 2021 ; 371 (6532): 926-931
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  • Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1A #MMPMID33495306
  • White KM; Rosales R; Yildiz S; Kehrer T; Miorin L; Moreno E; Jangra S; Uccellini MB; Rathnasinghe R; Coughlan L; Martinez-Romero C; Batra J; Rojc A; Bouhaddou M; Fabius JM; Obernier K; Dejosez M; Guillen MJ; Losada A; Aviles P; Schotsaert M; Zwaka T; Vignuzzi M; Shokat KM; Krogan NJ; Garcia-Sastre A
  • Science 2021[Feb]; 371 (6532): 926-931 PMID33495306show ga
  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral proteins interact with the eukaryotic translation machinery, and inhibitors of translation have potent antiviral effects. We found that the drug plitidepsin (aplidin), which has limited clinical approval, possesses antiviral activity (90% inhibitory concentration = 0.88 nM) that is more potent than remdesivir against SARS-CoV-2 in vitro by a factor of 27.5, with limited toxicity in cell culture. Through the use of a drug-resistant mutant, we show that the antiviral activity of plitidepsin against SARS-CoV-2 is mediated through inhibition of the known target eEF1A (eukaryotic translation elongation factor 1A). We demonstrate the in vivo efficacy of plitidepsin treatment in two mouse models of SARS-CoV-2 infection with a reduction of viral replication in the lungs by two orders of magnitude using prophylactic treatment. Our results indicate that plitidepsin is a promising therapeutic candidate for COVID-19.
  • |*COVID-19 Drug Treatment[MESH]
  • |Adenosine Monophosphate/analogs & derivatives/pharmacology/therapeutic use[MESH]
  • |Alanine/analogs & derivatives/pharmacology/therapeutic use[MESH]
  • |Animals[MESH]
  • |Antiviral Agents/*pharmacology/therapeutic use[MESH]
  • |COVID-19/prevention & control/virology[MESH]
  • |Coronavirus Nucleocapsid Proteins/biosynthesis/genetics[MESH]
  • |Depsipeptides/administration & dosage/*pharmacology/therapeutic use[MESH]
  • |Drug Evaluation, Preclinical[MESH]
  • |Female[MESH]
  • |HEK293 Cells[MESH]
  • |Humans[MESH]
  • |Lung/virology[MESH]
  • |Mice[MESH]
  • |Mice, Inbred C57BL[MESH]
  • |Mutation[MESH]
  • |Peptide Elongation Factor 1/*antagonists & inhibitors[MESH]
  • |Peptides, Cyclic[MESH]
  • |Phosphoproteins/biosynthesis/genetics[MESH]
  • |RNA, Viral/biosynthesis/genetics[MESH]
  • |SARS-CoV-2/*drug effects/genetics/physiology[MESH]


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