Whole-genome and mitogenome based in silico analysis of select Plasmodium and identification of a novel drug molecule against the malaria parasite

Abstract

Malaria, caused by a parasite known as Plasmodium, is one of the leading causes of death, worldwide, especially in the third world countries of Africa and Asia. Plasmodium does not only infect humans but also reptiles, birds and other mammals. However, they are the secondary hosts for this parasite. The primary host of Plasmodium is female Anopheles mosquitoes. Long term researchers have formulated drugs against this deadly pathogen but the current emergence of multi-drug resistance strains of Plasmodium has created a recurring concern. Identification of new drug molecules and understanding their mechanism of action is an urgent need to combat this battle. However, for that, we need to first understand the genomic strategies taken up by Plasmodium to survive the host immune system. With the advancement of high-throughput sequencing techniques, the whole genomes of Plasmodium have been sequenced which can help us in advancing our strategies against Plasmodium. In this study, we performed a thorough analysis of the genomic features of Plasmodium along with its evolution. This revealed a codon biased co-evolution among the parasite and respective hosts. Reverse ecology and protein-protein interactions were studied among Plasmodium and Homo sapiens revealing a complex biological interaction among them governing the host-parasite interaction as well as drug resistance capability among Plasmodium. The molecular docking and simulation studies have found a new drug-target site within mitogenome coding proteins. Those sites were targeted with Cymbopogonol, a phyto-compound derived from Cymbopogon (Lemongrass). Along with Cymbopogonol few other Cymbopogon derived compounds were also found to be effective as new anti-malarial drug molecules. This is the first report on the effect of Cymbopogon derived compounds on Plasmodium and is open for a clinical trial.