Exploring novel therapeutic strategies against vivax malaria through an integrated computational investigation to inhibit the merozoite surface protein−1 of Plasmodium vivax

Abstract

The obligate intra-erythrocytic protozoan parasite of the Plasmodium genus accounts for the manifestation of malaria, a life-threatening illness that is responsible for approximately 660,000 cases of worldwide annual mortality. In addition, resistance of the Plasmodium parasite to the conventionally used drug, artemisinin, contributes to 219 million of newly reported cases each year. Although, Plasmodium falciparum is responsible for the majority of the mortality cases of malaria, Plasmodium vivax is also known to contribute greatly towards the malaria related morbidities particularly in Asia and Latin America. In this study, we have used two different computational approaches aimed at establishing concepts for advanced therapeutics development against vivax malaria by targeting the surface antigen, merozoite surface protein-1 (MSP-1). Computational siRNA designing against MSP-1 resulted in a total of four non-immunogenic candidate siRNAs, out of which one siRNA candidate (siRNA 05) was found to exhibit a thermodynamically stable and feasible tertiary structure after being rationally validated following corroboration with a plethora of algorithms. Additionally, molecular docking analysis unraveled three anti-parasitic peptides named AP02283, AP02285 and AP00101 to exhibit considerable binding affinity with MSP-1, thus providing an apparent indication of their anti-malarial property. MD simulation reveals AP02283 as the best peptide candidate against MSP-1. However, irrespective of the prospective magnitude of these in-silico findings, the results require extensive validation by further rigorous laboratory experiments involving both in-vitro and in-vivo approaches.

Keywords

• Merozoite surface protein-1
• Computational approach
• siRNA designing
• Molecular docking
• Molecular dynamics
• Anti-malarial peptide