Abstract
Chikungunya virus (CHIKV) is a re-emerging mosquito-borne alphavirus that has recently engendered large epidemics around the world. There is no specific antiviral for treatment of patients infected with CHIKV, and development of compounds with significant anti-CHIKV activity that can be further developed to a practical therapy is urgently required. Andrographolide is derived from Andrographis paniculata, a herb traditionally used to treat a number of conditions including infections. This study sought to determine the potential of andrographolide as an inhibitor of CHIKV infection. Andrographolide showed good inhibition of CHIKV infection and reduced virus production by approximately 3log10 with a 50% effective concentration (EC50) of 77 μM without cytotoxicity. Time-of-addition and RNA transfection studies showed that andrographolide affected CHIKV replication and the activity of andrographolide was shown to be cell type independent. This study suggests that andrographolide has the potential to be developed further as an anti-CHIKV therapeutic agent.
Highlights
Strains of Chikungunya virus (CHIKV) with the substitution of a valine instead of the normal alanine at position 226 of the CHIKV E1 protein (E1 A226V)
Given the traditional usage of Andrographis paniculata to treat infections, this study sought to determine whether the principal bioactive ingredient possessed detectable anti-CHIKV activities
Cytotoxicity of andrographolide in the range 1–100 μ M was evaluated twice independently using the MTT assay at 24 hrs post-treatment (Supplemental Figure S1) and the alamarBlue assay at 24, 36 and 48 hr post treatment (Supplemental Figure S2)
Summary
Strains of CHIKV with the substitution of a valine instead of the normal alanine at position 226 of the CHIKV E1 protein (E1 A226V). Andrographolide, a bicyclic diterpenoid lactone is believed to be the main bioactive ingredient with potential anti-inflammatory and hepatoprotective effects[25]. Given the traditional usage of Andrographis paniculata to treat infections, this study sought to determine whether the principal bioactive ingredient (andrographolide) possessed detectable anti-CHIKV activities. In addition a non-relevant cell line previously used in evaluating anti-CHIKV compounds[29], BHK-21, was investigated. Andrographolide showed good potency in inhibiting CHIKV replication with no marked cytotoxicity in a cell culture system. These results suggest that andrographolide has significant potential for further development as an anti-CHIKV agent
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