Dhaneswar Prusty

Despite the continuous efforts to implement improved preventive measures for malaria, the World Health Organization has been reporting the rise of malaria's morbidity for the last five years. The primary cause of malaria treatment failure is the emerging resistance towards all most all front line antimalarials. The requirements for developing new antimalarials to support the current therapeutics include biochemical characterization of novel drug targets, identification of lead compounds for combination therapy, and the development of antimalarial therapeutics strategies from clinical drug libraries. Therefore, our lab research is extended from identifying novel targets to the identification of new drugs through high throughput screening.

Drug library and Natural compound screen to identify potent antimalarial agents

The prolonged timeline and enormous investment required for new drug discovery are significant obstructions to the formulation of therapies for neglected diseases. In this context, my laboratory focuses on the virtual high-throughput screening and validation of lead compounds in parasite culture of different drug libraries and natural compounds for malaria treatment. My earlier studies on nicotinamide and acriflavine in this direction are quite encouraging. We have some significant leads in discovering polypharmacological compounds in virtual screening, which we are carrying forward testing against chloroquine-sensitive and multidrug-resistant parasites. If everything goes fine will be further tested in animal models.

Rational approaches for the use of antibiotic scaffolds against the malaria parasite

The malaria parasite possesses a non-photosynthetic plastid called apicoplast that serves as an operational site for many indispensable biochemical pathways. I have identified and characterized some key players of the bacterial type DNA replication process of the apicoplast. Because the apicoplast's prokaryotic housekeeping functions are radically different from human metabolism, they are promising drug targets. Compounds that are meant to target bacterial housekeeping functions have been shown to have antimalarial properties. However, the proteins of apicoplast housekeeping functions retain significant differences in sequence and biochemical properties. So my lab is currently exploring specific inhibitors that target precisely the apicoplast housekeeping functions to provide a good source of leads for new malaria drugs.

Biochemical analysis of transcription machinery of Plasmodium  apicoplast

Among different antibiotics, rifampicin, supposed to target a putative bacterial type RNA polymerase of apicoplast, was the fastest-acting and most potent. Despite the importance of apicoplast transcription, little is known about the molecular machine "RNA polymerase" of apicoplast transcription.  It is also not known how the process is initiated and regulated. Therefore, My lab focuses on the structural and functional characterization of the apicoplast RNA polymerase that will definitely reveal many enigmatic features of apicoplast transcription and potential new drug leads for malaria.

Antiviral drug discovery by virtual screening and in vitro assays

In the COVID-19 pandemic, we expanded our research in discovering new antiviral compounds against SARS CoV-2. Our chemical system biology approach could identify many lead multi-targeting natural and FDA compounds. We are in the process of establishing various virus-free in vitro assays and cell culture assays to strengthen our research in the direction of antiviral compound discovery.