Implications of Fragment-Based Drug Discovery in Tuberculosis and HIV.

Abstract

Tuberculosis (TB) remains a global health problem and the emergence of HIV has further worsened it. Long chemotherapy and the emergence of drug-resistance strains of Mycobacterium tuberculosis as well as HIV has aggravated the problem. This demands urgent the need to develop new anti-tuberculosis and antiretrovirals to treat TB and HIV. The lack of diversity in drugs designed using traditional approaches is a major disadvantage and limits the treatment options. Therefore, new technologies and approaches are required to solve the current issues and enhance the production of drugs. Interestingly, fragment-based drug discovery (FBDD) has gained an advantage over high-throughput screenings as FBDD has enabled rapid and efficient progress to develop potent small molecule compounds that specifically bind to the target. Several potent inhibitor compounds of various targets have been developed using FBDD approach and some of them are under progression to clinical trials. In this review, we emphasize some of the important targets of mycobacteria and HIV. We also discussed about the target-based druggable molecules that are identified using the FBDD approach, use of these druggable molecules to identify novel binding sites on the target and assays used to evaluate inhibitory activities of these identified druggable molecules on the biological activity of the targets.