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Antiviral activity of a synthesized shikonin ester against influenza A (H1N1) virus and insights into its mechanism.

Antiviral activity of a synthesized shikonin ester against influenza A (H1N1) virus and insights into its mechanism.
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Zhang Y, Han H, Qiu H, Lin H, Yu L, Zhu W, Qi J, Yang R, Pang Y, Wang X, Lu G, Yang Y,


Zhang Y, Han H, Qiu H, Lin H, Yu L, Zhu W, Qi J, Yang R, Pang Y, Wang X, Lu G, Yang Y, (click to view)

Zhang Y, Han H, Qiu H, Lin H, Yu L, Zhu W, Qi J, Yang R, Pang Y, Wang X, Lu G, Yang Y,

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Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2017 07 0593() 636-645 pii S0753-3322(17)30369-4
Abstract

This study aimed to examine the antiviral effects of shikonin ester ((R)-1-(5, 8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl3-(1H- indol-3-yl) propanoate (PMM-034) against influenza A (H1N1) virus. We investigated PMM-034 anti-H1N1 activity and its effect on caspase 3 gene expression during cellular apoptosis after influenza virus infection in vitro. Neuraminidase (NA) inhibition was assessed in comparison with oseltamivir in the influenza virus standard strains A/PR/8/34 to understand the viral mechanism. MDCK and A549 cells were used to investigate influenza viral infection and the structure-activity relationship between PMM-034 and NA was evaluated by pharmacophore-based docking modeling. The production of viral protein was tested by western blot. A/PR/8/34 induced cell inhibition but this was reduced by PMM-034 to 16μg/mL and this showed a selective index of 10mM. PMM-034 inhibited NA in a dose dependent manner, similar to oseltamivir inhibition. A sharp decrease in viral nucleocapsid protein mRNA was observed in infected cells after treatment with PMM-034. Apoptosis of infected A459 cells was inhibited by PMM-034 with decreased caspase 3 levels. ARG 118, ARG 152, ARG 371 and GLU 227 in the binding pocket of NA bound to PMM-034 in the docking model. Taken together, these results suggest PMM-034 shikonin ester blocked H1N1 infection and might be a potential anti-H1N1 drug.

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