2. Academic Validation
  3. 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

  • Biomed Pharmacother. 2017 Sep;93:636-645. doi: 10.1016/j.biopha.2017.06.076.
Yahan Zhang 1,  Hongwei Han 2,  Hanyue Qiu 2,  Hongyan Lin 2,  Lugang Yu 3,  Wanzhan Zhu 3,  Jinliang Qi 4,  Rongwu Yang 2,  Yanjun Pang 2,  Xiaoming Wang 5,  Guihua Lu 6,  Yonghua Yang 7
Affiliations

Affiliations

  • 1 State Key Laboratory of Pharmaceutical Biotechnology, NJU-NJFU Joint Institute of Plant Molecular Biology, Nanjing University, Nanjing 210023, China; Suzhou Industrial Park Center for Disease Control and Prevention, Suzhou 215000, China.
  • 2 State Key Laboratory of Pharmaceutical Biotechnology, NJU-NJFU Joint Institute of Plant Molecular Biology, Nanjing University, Nanjing 210023, China.
  • 3 Suzhou Industrial Park Center for Disease Control and Prevention, Suzhou 215000, China.
  • 4 State Key Laboratory of Pharmaceutical Biotechnology, NJU-NJFU Joint Institute of Plant Molecular Biology, Nanjing University, Nanjing 210023, China; Co-Innovation Center for Sustainable Forestry in Southern China, Nanjing Forestry University, Nanjing 210037, China.
  • 5 State Key Laboratory of Pharmaceutical Biotechnology, NJU-NJFU Joint Institute of Plant Molecular Biology, Nanjing University, Nanjing 210023, China; Co-Innovation Center for Sustainable Forestry in Southern China, Nanjing Forestry University, Nanjing 210037, China. Electronic address: wangxm07@nju.edu.cn.
  • 6 State Key Laboratory of Pharmaceutical Biotechnology, NJU-NJFU Joint Institute of Plant Molecular Biology, Nanjing University, Nanjing 210023, China; Co-Innovation Center for Sustainable Forestry in Southern China, Nanjing Forestry University, Nanjing 210037, China. Electronic address: guihua.lu@nju.edu.cn.
  • 7 State Key Laboratory of Pharmaceutical Biotechnology, NJU-NJFU Joint Institute of Plant Molecular Biology, Nanjing University, Nanjing 210023, China; Co-Innovation Center for Sustainable Forestry in Southern China, Nanjing Forestry University, Nanjing 210037, China. Electronic address: yangyh@nju.edu.cn.
PMID: 28688289 DOI: 10.1016/j.biopha.2017.06.076
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.

Keywords

Antiviral agents; Drug discovery; Esters; Influenza virus H1N1 sub-type; Shikonin.

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