In silico modeling and virtual screening for identification of inhibitors for SWP12 and SWP30 in Nosema bombycis

Bombyx mori, an insect, is of great economic value, widely known for the production of silk. Nosema bombycis, an intracellular parasite, often infects it and causes a fatal disease - Pebrine which affects the development of the worm. The infected larvae of the silkworms are coated with a brown spot. It also causes loss of appetite, makes them sluggish and opaque, ultimately resulting in death. The proteins studied here are SWP12 and SWP30, both of which are an exosporal protein found in N.bombycis. SWP12 is a chitin-binding protein, involved in the development of spore walls. It acts as an important surface protein of N. bombycis. It facilitates microsporidial spore maintenance. NbSWP12 is located on the cytoskeleton as well as the spore coat of N. bombycis. The developmental stage at which it is expressed is not known. SWP30 plays a role in sporulation, leading to the formation of a cellular spore. It is capable of binding to deproteinated chitin spore coats (DSCSs). It is expressed in the spore wall and synthesized during sporogony. This study deals with pebrine infection in Bombyx mori due to the pathogen Nosema bombycis. The infection leads to poor quality of silk production and loss of batches due to high mortality upon infection. The structure of spore wall protein present on N. bombycis was built by employing homology modelling technique. Virtual screening was conducted on a ligand library to discover lead compounds. 100ns molecular dynamics (MD) simulation was performed. RMSD, RMSF and Radius of Gyration were analyzed to determine the stability of the modeled protein and protein ligand complexes. Through virtual screening and docking studies, ligand molecules ZINC000067910920 and ZINC000035458200 were obtained as a potential drug-like molecule.