Chikungunya virus (CHIKV) is a mosquito-borne pathogen responsible for major outbreaks of febrile arthralgia in humans. No antiviral treatment is currently available.The viral genome encodes four non-structural proteins (nsPs), which could represent suitable antiviral targets. The nspP2 protein in particular is a protease essential for the formation of the mature nsPs.A virtual screening study of a library of small molecule compounds, performed on the structure of a homology model of the CHIKV nsP2, allowed the identification of one hit which prevented virus-induced cell death at low �M concentration.Optimisation studies guided the selection of structural analogues of the original active molecule, which were found to inhibit the virus cytotoxic effect in Vero cells.Based on these results, different series of new derivatives were designed and synthesised. Inhibition of virus-induced cell death was evaluated for the new compounds and several showed �M activity.

Design, synthesis, and evaluation of novel anti-CHIKV compounds

245th National Meeting (2013)

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