Journal
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH
Volume 50, Issue 10, Pages -Publisher
ASSOC BRAS DIVULG CIENTIFICA
DOI: 10.1590/1414-431X20176586
Keywords
EV71; VP1; Shikonin ester derivatives PMM-034; Rhabdomyosarcoma cells; NF-kappa B
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Funding
- Program for Changjiang Scholars and Innovative Research Team in University [IRT_14R27]
- National Natural Science Foundation of China [31470384, 31171161, 31670298]
- Fundamental Research Funds for the Central Universities [020814380002]
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Human enterovirus 71 (EV71) is the major causative agent of hand, foot, and mouth disease (HFMD), particularly in infants and children below 4 years of age. Shikonin is a bioactive compound with anti-inflammatory, antiviral, and antibacterial activities derived from the roots of the Chinese medicinal herb Lithospermum erythrorhizon. This study aimed to examine the antiviral activity of PMM-034, a shikonin ester derivative, against EV71 in rhabdomyosarcoma (RD) cells. Cytotoxicity of PMM-034 on RD cells was determined using WST-1 assay. Dose- and time-dependent effects of PMM-034 on EV71 replication in RD cells were determined using plaque reduction assay. mRNA expression levels of EV71/VP1 and pro-inflammatory cytokines (IL-1 beta, IL-6, IL-8, and TNF-alpha) were determined by real-time RT-PCR, and EV71/VP1 and phospho-p65 protein expressions were determined by western blot analysis. PMM-034 exhibited only weak cytotoxicity against RD cells. However, PMM-034 exhibited significant antiviral activity against EV71 in RD cells with 50% inhibitory concentration of 2.31 mu g/mL. The VP1 mRNA and protein levels were significantly reduced in cells treated with PMM-034. Furthermore, relative mRNA expression levels of IL-1 beta, IL-6, IL-8, and TNF-alpha significantly decreased in the cells treated with PMM-034, while the phospho-p65 protein expression was also significantly lower in the treated cells. These results indicated that PMM-034 suppressed the expressions of cytokines in RD cells, exhibiting antiviral activity against EV71, as evidenced by the reduced VP1 mRNA and protein levels in PMM-034-treated cells. Thus, PMM-034 is a promising candidate for further development as an EV71 inhibitor.
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