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Lycorine, a non-nucleoside RNA dependent RNA polymerase inhibitor, as potential treatment for emerging coronavirus infections.
- Source :
-
Phytomedicine : international journal of phytotherapy and phytopharmacology [Phytomedicine] 2021 Jun; Vol. 86, pp. 153440. Date of Electronic Publication: 2020 Dec 16. - Publication Year :
- 2021
-
Abstract
- 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'Hér.) Herb. and has various pharmacological bioactivities including antiviral function.<br />Purpose: We investigated the direct-inhibiting action of lycorine on CoV's RdRp, as potential treatment for emerging CoV infections.<br />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.<br />Results: Lycorine efficiently inhibited these CoVs with IC <subscript>50</subscript> values of 2.123 ± 0.053, 1.021 ± 0.025, and 0.878 ± 0.022 μM, respectively, comparable with anti-CoV effects of remdesivir. Lycorine directly inhibited MERS-CoV RdRp activity with an IC <subscript>50</subscript> of 1.406 ± 0.260 μM, compared with remdesivir's IC <subscript>50</subscript> value of 6.335 ± 0.731 μM. 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).<br />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.<br /> (Copyright © 2020 The Author(s). Published by Elsevier GmbH.. All rights reserved.)
- Subjects :
- Adenosine Monophosphate analogs & derivatives
Alanine analogs & derivatives
Animals
Chlorocebus aethiops
Hydrogen Bonding
Middle East Respiratory Syndrome Coronavirus drug effects
Molecular Docking Simulation
Severe acute respiratory syndrome-related coronavirus drug effects
Vero Cells
Viral Proteins
Amaryllidaceae Alkaloids pharmacology
Antiviral Agents pharmacology
Phenanthridines pharmacology
RNA-Dependent RNA Polymerase antagonists & inhibitors
SARS-CoV-2 drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1618-095X
- Volume :
- 86
- Database :
- MEDLINE
- Journal :
- Phytomedicine : international journal of phytotherapy and phytopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 33376043
- Full Text :
- https://doi.org/10.1016/j.phymed.2020.153440