Comparative Transcriptome Analysis of Different Stages of Plasmodium Falciparum for Discovery of Vaccine and Drug Candidates

Abstract

newline ix newlineABSTRACT newlineMalaria is a life-threatening disease, which causes huge economical/physical burden on humans. There were 219 million cases of malaria in 2017 and 435 000 death were reported due to it. It is a widespread disease found in Asia, Europe, and America. But no widely used vaccines are available for malaria parasites despite so many efforts to develop them. The condition is becoming worst as the parasite has developed resistance to all available drugs, except have been shown resistance in some cases. Lot of research has been carried out proteomic and sequenced genomes of different pathogenic Plasmodium species are now available. Researcher have carried out study on genomic, proteomic and transcriptome of different strain of Plasmodium species and strains to understand complex pathology of pathogens as well as to discover therapeutics. Limited numbers of studies on differential expression of transcriptome on different stages of Plasmodium have been reported. Hence, to target all stages of Plasmodium simultaneously comparative transcriptome analysis of different stages was carried out and 44 commonly expressed proteins from different stages of Plasmodium were identified. For vaccine design different analysis important for proteins vaccine candidate can be done which include identification of domain architecture, calculation of antigenicity, and mapping of different type of epitopes. Conservation of these proteins in human infecting Plasmodium species was also studied. These proteins can be taken as drug targets and/or vaccine candidates in further experimentation against malaria. One important protein Actin I which was expressed in all human stages and proposed as drug target in literature was selected of structure based drug design study. Actin protein is one of the important protein in Plasmodium falciparum playing various important roles like transport, cell motility, cell division and shape determination. Top ranking molecules according to docking result against Actin I were considered as potential lead molecules. Further these potential lead molecules were subjected for pharmacokinetic study to investigate important drug parameters Overall, this study provides a basis for further taking these potential lead molecules for in vitro and in vivo experimentations for designing better drugs and exploit Actin I as a potential drug target.