Lycorine, a non-nucleoside RNA dependent RNA polymerase inhibitor, as potential treatment for emerging coronavirus infections.
Phytomedicine
; 86: 153440, 2021 Jun.
Article
en En
| MEDLINE
| ID: mdl-33376043
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.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 IC50 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 IC50 of 1.406 ± 0.260 µM, compared with remdesivir's IC50 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).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.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Antivirales
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Fenantridinas
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ARN Polimerasa Dependiente del ARN
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Alcaloides de Amaryllidaceae
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SARS-CoV-2
Límite:
Animals
Idioma:
En
Revista:
Phytomedicine
Asunto de la revista:
TERAPIAS COMPLEMENTARES
Año:
2021
Tipo del documento:
Article