Cloning, functional characterization and screening of potential inhibitors forChilo partelluschitin synthase A usingin silico,in vitroandin vivoapproaches

Chitin synthase (CHS) is one of the crucial enzymes that play an essential role in chitin synthesis during the molting process, and it is considered to be the specific target to control insect pests. Currently, there are no potent inhibitors available in the market, which specifically target this enzyme. Pyrimidine nucleoside peptide, nikkomycin Z, binds to nucleotide-binding sites of fungal and insect CHS. But, their mode of action is still fragmentary due to the lack of a 3Dstructure of CHS.Chilo partellusis a severe pest insect of major food crops such as maize and sorghum, in an attempt to target integument expressed cuticularCpCHS. TheCpChsAcDNA was cloned, and subsequently, their developmental and tissue-specific expression was studied. The 3D structure of the CHS catalytic domain was modeled, after which natural compounds were screened using a virtual screening workflow and resulted in the identification of five hit molecules. Molecular dynamics simulations were performed to investigate the dynamics and interactions of hits withCpCHS. The obtained results revealed that the compounds kasugamycin, rutin and robinin could act as potent inhibitors ofCpCHS. All three molecules were observed to significantly reduce the chitin production as validated usingin vitroandin vivostudies. Thus, this study aims to provide a set of novel inhibitor molecules againstCpCHS for controlling the pest population. Communicated by Ramaswamy H. Sarma