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10.1016/j.phymed.2020.153440

http://scihub22266oqcxt.onion/10.1016/j.phymed.2020.153440
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33376043!7738280!33376043
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suck abstract from ncbi


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pmid33376043      Phytomedicine 2021 ; 86 (ä): 153440
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  • Lycorine, a non-nucleoside RNA dependent RNA polymerase inhibitor, as potential treatment for emerging coronavirus infections #MMPMID33376043
  • Jin YH; Min JS; Jeon S; Lee J; Kim S; Park T; Park D; Jang MS; Park CM; Song JH; Kim HR; Kwon S
  • Phytomedicine 2021[Jun]; 86 (ä): 153440 PMID33376043show ga
  • BACKGROUND: Highly effective novel treatments need to be developed to suppress emerging coronavirus (CoV) infections such as COVID-19. The RNA dependent RNA polymerase (RdRp) among the viral proteins is known as an effective antiviral target. Lycorine is a phenanthridine Amaryllidaceae alkaloid isolated from the bulbs of Lycoris radiata (L'Her.) Herb. and has various pharmacological bioactivities including antiviral function. PURPOSE: We investigated the direct-inhibiting action of lycorine on CoV's RdRp, as potential treatment for emerging CoV infections. METHODS: We examined the inhibitory effect of lycorine on MERS-CoV, SARS-CoV, and SARS-CoV-2 infections, and then quantitatively measured the inhibitory effect of lycorine on MERS-CoV RdRp activity using a cell-based reporter assay. Finally, we performed the docking simulation with lycorine and SARS-CoV-2 RdRp. RESULTS: Lycorine efficiently inhibited these CoVs with IC(50) values of 2.123 +/- 0.053, 1.021 +/- 0.025, and 0.878 +/- 0.022 muM, respectively, comparable with anti-CoV effects of remdesivir. Lycorine directly inhibited MERS-CoV RdRp activity with an IC(50) of 1.406 +/- 0.260 muM, compared with remdesivir's IC(50) value of 6.335 +/- 0.731 muM. In addition, docking simulation showed that lycorine interacts with SARS-CoV-2 RdRp at the Asp623, Asn691, and Ser759 residues through hydrogen bonding, at which the binding affinities of lycorine (-6.2 kcal/mol) were higher than those of remdesivir (-4.7 kcal/mol). CONCLUSIONS: Lycorine is a potent non-nucleoside direct-acting antiviral against emerging coronavirus infections and acts by inhibiting viral RdRp activity; therefore, lycorine may be a candidate against the current COVID-19 pandemic.
  • |Adenosine Monophosphate/analogs & derivatives[MESH]
  • |Alanine/analogs & derivatives[MESH]
  • |Amaryllidaceae Alkaloids/*pharmacology[MESH]
  • |Animals[MESH]
  • |Antiviral Agents/*pharmacology[MESH]
  • |Chlorocebus aethiops[MESH]
  • |Hydrogen Bonding[MESH]
  • |Middle East Respiratory Syndrome Coronavirus/drug effects[MESH]
  • |Molecular Docking Simulation[MESH]
  • |Phenanthridines/*pharmacology[MESH]
  • |RNA-Dependent RNA Polymerase/*antagonists & inhibitors[MESH]
  • |SARS-CoV-2/*drug effects[MESH]
  • |Severe acute respiratory syndrome-related coronavirus/drug effects[MESH]
  • |Vero Cells[MESH]


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