An In Silico Approach for Targeting Plasmodium Phosphatidylinositol 4-Kinase to Eradicate Malaria
Accomplishing the destination of malaria evacuation will depend upon directing Plasmodium pathways necessity throughout all life stages. Here, we selected a lipid kinase, phosphatidylinositol 4-kinase (PI4K), as the potential drug target, In order to achi
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Abstract Accomplishing the destination of malaria evacuation will depend upon directing Plasmodium pathways necessity throughout all life stages. Here, we selected a lipid kinase, phosphatidylinositol 4-kinase (PI4K), as the potential drug target, In order to achieve a novel antimalarial compound that inhibits the intracellular development of multiple Plasmodium species at each stage of infection in the vertebrate host. Virtual screening was performed against more than thousands of compounds from ZINC database to get some potent natural compounds which are able to inhibit PI4K. Binding affinity of screened compounds was compared with well-known inhibitor like Primaquine as a reference molecule, by analyzing their docking score and binding efficiency with the receptor. ADMET properties of the obtained screened compounds were analyzed to check drug like property. Based on the aforementioned analysis, it has been suggested that these screened potent compounds are capable to inhibit PI4K for the prevention, treatment and elimination of malaria. Keywords Phosphatidylinositol 4-kinase (PI4K)
Virtual screening ADME/T
1 Introduction To eradicate malaria, broadly acting medicines must be formulated that therapeutic the diagnostic asexual blood stage, clear the coming before liver phase transmission that can induce relapses and block parasite infection to mosquitoes [1]. Relapse prevention is particularly significant for P. falciparum and P. vivax, which makes
K.K. Chaudhary S.K. Gupta N. Mishra (&) Division of Bioinformatics and Applied Science, Indian Institute of Information Technology, Allahabad 211012, UP, India e-mail: [email protected] © Springer Science+Business Media Singapore 2016 R.K. Choudhary et al. (eds.), Advanced Computing and Communication Technologies, Advances in Intelligent Systems and Computing 452, DOI 10.1007/978-981-10-1023-1_28
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intra-hepatic hypnozoites that, can remain for year earlier reinitiating growth and activating blood stage infection. Primaquine is the drug of choice for treating malaria and only accredited marketed antimalarial drug capable of eradicating the hypnozoite reservoir and perform a radicalcure. Nevertheless, side-effects and weak activity against blood stages prevent widespread usage of primaquine [2]. Subsequently primaquine’s target and mechanism of action are not well known, the explore for new revolutionary therapeutic drugs has been limited to concerned analogues, such as Tafenoquine [3]. There is a clear demand for druggable and chemically related validated targets that are necessity in all lifecycle stages of the malaria parasite. Here we describe that a parasite phosphatidylinositol 4-kinase, anomni present eukaryotic enzyme that phosphorylates lipids to govern intracellular signaling and trafficking, is inhibited by screened molecules. In blood stages, inhibitors block a late step in parasite growth by interrupting plasma membrane ingression throughout growing daughter merozoites. This probably stems from varied phosphatid
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