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CorA as anthelmintic - Natural product as antibiotic for the treatment of filariasis

Human filariasis (elephantiasis and river blindness) is caused by the nematodes W. bancrofti and O. volvulus, transmitted via blood sucking insects. The worms harbour the bacterial endosymbiont Wolbachia, which is essential for embryogenesis, larval development and adult worm survival.

Corallopyronin A (CorA) has efficacy against the intracellular Wolbachia of filarial nematodes. Experiments in mice show that all worms were depleted of more than 98% of their Wolbachia, resulting in blocked larval development and phenotypically altered worms. The results indicate the potential of CorA to effectively eliminate filarial disease by killing larvae as well as adult worms with one (maximum of two) treatment regimens. No toxicity against eukaryotic cells was detected. Preliminary pharmacokinetic data show that the antibiotic is amenable to oral administration. CorA is a non-competitive inhibitor of bacterial DNA-dependent RNA polymerase, with a different mode of action from rifampicin.

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