IN SILICO DESIGNING AND ANALYSIS OF INHIBITORS AGAINST TARGET PROTEIN OF MALARIA

Abstract

Malaria, initiated by apicomplexan parasite, is an old disease and continues to be a major public health threat in
many countries. This article aims to present different aspects of malaria including causes, pathogenesis, prevention,
and treatment in an articulate and comprehensive manner and it causes high levels of morbidity and mortality in
human beings worldwide. The development of new molecular tools as well as the use of next-generation sequencing
(NGS) technologies and novel bioinformatics approaches has improved our knowledge of malarial epidemiology,
diagnosis, treatment, vaccine development, and surveillance strategies.The Plasmodium falciparum is the most
dangerous species that can infect human. The enzyme hypoxanthine-guanine phosphorybosyltransferase (HGPRT)
in the malarial parasite Plasmodium falciparum (Pf) is central to the salvage pathway for purine nucleotide
biosynthesis and is a potential antimalarial chemotherapeutic target. As with all metabolic pathways, serious
problems occur if steps in the pathway are blocked. Some people inherit a rare defective version of HGPRT, which
leads to a serious illness termed Lesch-Nyhan syndrome. Vector and parasite drug resistance are two major
challenges for malaria control that require special attention. Artemisinins are sesquiterpene lactones, and has been
recently approved for the treatment of malaria due to its endoperoxidase properties. This approach also estimates the
ligand-receptor binding free energy by evaluating critical phenomena involved in the intermolecular recognition
process. Prodrugs of these compounds have IC50 values in the 4-6 mM range in antimalarial cellbased assays,
making them attractive compounds for further development as antimalarial drug leads. The purpose of this review is
to examine current molecular docking strategies used in drug discovery and medicinal chemistry, exploring the
advances in the field and the role played by the integration of structure- and ligand-based methods.