Filarial Phosphoglycerate Kinase as Potential Drug Target

Abstract

newline Lymphatic filariasis is one of the most pervasive diseases of developing world. It affects over 120 million people in 72 endemic countries worldwide. Although the disease does not result in immediate mortality, the associated morbidity is believed to cause significant disability leading to impediment in socio-economic development. Human lymphatic filarial parasites are long lived organisms, which persist in host despite vigorous immune response. About 76 million people are carrying the parasites in their blood with no clinical symptoms. Within the last few years, the currently available antifilarial drugs, diethylcarbamazine and albendazole are principally microfilaricidal with little or negligible effect on adult filarial parasites. However, the treatment results into reappearance of microfilariae after a period of therapy. Therefore, there is an urgent need for the identification and chemotherapeutic characterization of new drug targets that could be used to develop potential adulticides. newlinePGK is a monomeric enzyme consists of 415-residues, catalyses the conversion of 1, 3-bisphosphoglycerate to 3-phosphoglycerate, first substrate-level phosphorylation reaction in the glycolytic pathway for production of ATP by using magnesium as a cofactor. In the mammalian nucleus, PGK influences DNA replication and repair and has been identified as a host factor necessary for in vitro mRNA synthesis of the Sendai virus. After vaccination with such an antigens, the probability of eliciting an autoimmune response is high. In case of Fasciola hepatica PGK has different antigenic epitopes as compared to host PGK, so antibodies produced against parasitic PGK do not reacts with host PGK. The PGK has already been explored in helminths such as Fasciola hepatica as potential vaccine candidate for controlling fasciolosis