Abstract
The mosquito-borne chikungunya virus (CHIKV) causes chikungunya fever, with clinical presentations such as severe back and small joint pain, and debilitating arthritis associated with crippling pains that persist for weeks and even years. Although there are several studies to evaluate the efficacy of drugs against CHIKV, the treatment for chikungunya fever is mainly symptom-based and no effective licensed vaccine or antiviral are available. Here, we investigated the antiviral activity of three types of flavonoids against CHIKV in vitro replication. Three compounds: silymarin, quercetin and kaempferol were evaluated for their in vitro antiviral activities against CHIKV using a CHIKV replicon cell line and clinical isolate of CHIKV of Central/East African genotype. A cytopathic effect inhibition assay was used to determine their activities on CHIKV viral replication and quantitative reverse transcription PCR was used to calculate virus yield. Antiviral activity of effective compound was further investigated by evaluation of CHIKV protein expression using western blotting for CHIKV nsP1, nsP3, and E2E1 proteins. Briefly, silymarin exhibited significant antiviral activity against CHIKV, reducing both CHIKV replication efficiency and down-regulating production of viral proteins involved in replication. This study may have important consequence for broaden the chance of getting the effective antiviral for CHIKV infection.
Highlights
Phylogenetic analysis shows that chikungunya virus (CHIKV) has three genotype variants; West African, East/Central/ South African (ECSA) and Asian[8]
Different non-cytotoxic concentrations of silymarin, kaempferol and quercetin were tested on CHIKV-infected Vero cells to find the effective compound
It was shown that 100 μ g/ml of silymarin significantly inhibited the CHIKV-cytopathic effect (CPE) presentation (P = 0 .0007) (Fig. 1a)
Summary
Phylogenetic analysis shows that CHIKV has three genotype variants; West African, East/Central/ South African (ECSA) and Asian[8]. Vector switching to A. albopictus became predominant due to the substitution of Alanine residue 226 to Valine residue in the CHIKV E1 protein (A226V)[13] This convergent mutation seems to be due to the selective pressure as the impact of different and new environment or ecosystem. The mechanism of actions of quercetin includes: enhancing the antiviral activity of interferon, binding to viral proteins, and interfering with viral nucleic acid synthesis by binding to the viral polymerases. Another flavonoid, kaempferol is active against HSV, human coronavirus and rotavirus replication[17]. Silymarin itself, is a complex of more than 7 flavonolignans (silybin A, silybin B, isosilybin A, isosilybin B, silychristin, isosilychristin and silydianin) and 1 flavonoid whereas silibinin is a semi-purified, commercially available fraction of silymarin, with an approximate 1:1 mixture of 2 diastereoisomeric compounds, silybin A and silybin B which are referred to in the literature as silibinin A and B19
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