Emerging strategies and challenges of molecular therapeutics in antileishmanial drug development

Molecular therapy refers to targeted therapies based on molecules which have been intelligently directed towards specific biomolecular structures and include small molecule drugs, monoclonal antibodies, proteins and peptides, DNA or RNA-based strategies, targeted chemotherapy and nanomedicines. Molecular therapy is emerging as the most effective strategy to combat the present challenges of life-threatening visceral leishmaniasis, where the successful human vaccine is currently unavailable. Moreover, current chemotherapy-based strategies are associated with the issues of ineffective targeting, unavoidable toxicities, invasive therapies, prolonged treatment, high treatment costs and the development of drug-resistant strains. Thus, the rational approach to antileishmanial drug development primarily demands critical exploration and exploitation of biochemical differences between host and parasite biology, immunocharacteristics of parasite homing, and host-parasite interactions at the molecular/cellular level. Following this, the novel technology-based designing and development of host and/or parasite-targeted therapeutics having leishmanicidal and immunomodulatory activity is utmost essential to improve treatment efficacy. Thus, the present review is focused on immunological and molecular checkpoint targets in host-pathogen interaction, and molecular therapeutic prospects for Leishmania intervention, and the challenges ahead.