• Qudsia Yousafi

• Hafsa Anwar

• Hamid Rashid

• Qurban Ali

• Muhammad Saad Khan

• Asim Mehmood

• Shahzad Saleem

• Muhammad Wasim Sajid

• Rida Irfan

• Ashir Masroor

Abstract

Mosquitoes, Aedes aegypti L. and Anopheles gambiae G. are very important insect vectors for transmission of infectious diseases like dengue and malaria. Extensive use of insecticides provided rapid control of these insect vectors but gradually they have developed insecticide resistance. Target site insensitivity is one the main reasons for insecticide resistance development. Development of new insecticides targeting different target sites can be a useful approach for management of insecticide resistance in insect pests. Chorion peroxidase inhibitors have been predicted by using computer aided drug designing (CAAD) approach. 3D structure of chorion peroxidase of A. aegypti and A. gambiae was predicted by using ITASSER and refined by 3Drefine and GalaxyWEB servers. Ligand binding sites were predicted by using 3DLigandSite, RaptorX and COACH servers. Ligands/Inhibitor compounds were obtained from literature and drug bank. Protein-ligand docking was performed by AutoDock Vina. The compounds with low binding energy and good interactions were selected for both species. Pharmacophore models were generated by using LigandScout. Screening of zinc library was performed against the features of designed pharmacophores. Top ten compounds with best pharmacophore fit score for each species were selected for docking with chorion peroxidase. Protein ligand interactions were determined through LIGPLOT. One lead compound showing lowest binding energy and best interactions was selected for each species, i.e., ZINC04581496 (A. aegypti) and ZINC15675298 (A. gambiae). Protein-Protein interaction was studied by STRING database to find the co-expressing proteins in network of chorion peroxidase. Ten interaction partners were found for A. aegypti while five for A. gambiae. These pharmacophore models may provide theoretical basis for designing effective insecticides for A. aegypti and A. gambiae control. The efficacy of computationally predicted lead molecules can be confirmed by testing in vitro and in vivo.

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