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Identification of potential modulator of Anopheles gambiae odorant binding protein 1 by hierarchical virtual screening and molecular dynamics

Abstract Malaria is a protozoan infection transmitted by the bite of the infected female mosquito belonging to the genus Anopheles spp., which causes more than 445 million annual deaths worldwide. Available drugs have serious adverse effects (e.g. blurred vision, hypotension and headache) and species-dependent efficacy. An alternative to overcome these problems involve the use of molecules with affinity to the Anopheles gambiae mosquito odor receptors, minimizing the reinfection process as well as reducing the problems related to pharmacological therapy. The vector control can interrupt the epidemiological cycle and, therefore, control the malaria incidence. In the olfactory pathway, odorant binding protein 1 acts on the first level of odor recognition on malarial vector and thus can be used to modulate mosquito behavior and development of new attracts or repellents. Thus, this study applied ligand-based (2D-chemical similarity) and structure-based (docking and molecular dynamics) computational approaches to prioritize potential olfactory modulators on natural products catalogs at ZINC15 database (n = 98,379). Hierarchical virtual screening prioritized a potential olfactory modulator (Z8217) against Anopheles gambiae odorant binding protein 1 (AgOBP1). Next, it was submitted to molecular dynamics routine to identify structural requirements and the interactions profile required for binding-site affinity. This promising natural compound can interact like experimental ligand and will be used in repellency assay to confirm its sensorial behavior. Communicated by Ramaswamy H. Sarma