A novel flavanone derivative inhibits dengue virus fusion and infectivity.
Antiviral Res
; 151: 27-38, 2018 03.
Article
em En
| MEDLINE
| ID: mdl-29360474
ABSTRACT
Dengue infection is a global burden affecting millions of world population. Previous studies indicated that flavanones were potential dengue virus inhibitors. We discovered that a novel flavanone derivative, 5-hydroxy-7-methoxy-6-methylflavanone (FN5Y), inhibited DENV2 pH-dependent fusion in cell-based system with strong binding efficiency to DENV envelope protein at K (P83, L107, K128, L198), K' (T48, E49, A50, L198, Q200, L277), X' (Y138, V354, I357), and Y' (V97, R99, N103, K246) by molecular dynamic simulation. FN5Y inhibited DENV2 infectivity with EC50s (and selectivity index) of 15.99⯱â¯5.38 (>6.25), and 12.31⯱â¯1.64 (2.23) µM in LLC/MK2 and Vero cell lines, respectively, and inhibited DENV4 at 11.70⯱â¯6.04 (>8.55) µM. CC50s in LLC/MK2, HEK-293, and HepG2 cell lines at 72â¯h were higher than 100⯵M. Time-of-addition study revealed that the maximal efficacy was achieved at early after infection corresponded with pH-dependent fusion. Inactivating the viral particle, interfering with cellular receptors, inhibiting viral protease, or the virus replication complex were not major targets of this compound. FN5Y could become a potent anti-flaviviral drug and can be structurally modified for higher potency using simulation to DENV envelope as a molecular target.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Antivirais
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Dengue
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Vírus da Dengue
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Flavanonas
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Internalização do Vírus
Limite:
Animals
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Humans
Idioma:
En
Revista:
Antiviral Res
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Tailândia