tetano
Editor, Senior Moderator
Biomed Pharmacother. 2017 Jul 5;93:636-645. doi: 10.1016/j.biopha.2017.06.076. [Epub ahead of print]
[h=1]Antiviral activity of a synthesized shikonin ester against influenza A (H1N1) virus and insights into its mechanism.[/h] Zhang Y[SUP]1[/SUP], Han H[SUP]2[/SUP], Qiu H[SUP]2[/SUP], Lin H[SUP]2[/SUP], Yu L[SUP]3[/SUP], Zhu W[SUP]3[/SUP], Qi J[SUP]4[/SUP], Yang R[SUP]2[/SUP], Pang Y[SUP]2[/SUP], Wang X[SUP]5[/SUP], Lu G[SUP]6[/SUP], Yang Y[SUP]7[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
Copyright ? 2017 Elsevier Masson SAS. All rights reserved.
[h=4]KEYWORDS:[/h] Antiviral agents; Drug discovery; Esters; Influenza virus H1N1 sub-type; Shikonin
PMID: 28688289 DOI: 10.1016/j.biopha.2017.06.076
[h=1]Antiviral activity of a synthesized shikonin ester against influenza A (H1N1) virus and insights into its mechanism.[/h] Zhang Y[SUP]1[/SUP], Han H[SUP]2[/SUP], Qiu H[SUP]2[/SUP], Lin H[SUP]2[/SUP], Yu L[SUP]3[/SUP], Zhu W[SUP]3[/SUP], Qi J[SUP]4[/SUP], Yang R[SUP]2[/SUP], Pang Y[SUP]2[/SUP], Wang X[SUP]5[/SUP], Lu G[SUP]6[/SUP], Yang Y[SUP]7[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
Copyright ? 2017 Elsevier Masson SAS. All rights reserved.
[h=4]KEYWORDS:[/h] Antiviral agents; Drug discovery; Esters; Influenza virus H1N1 sub-type; Shikonin
PMID: 28688289 DOI: 10.1016/j.biopha.2017.06.076