Computer aided virtual screening and selection of novel phytoligands against shigellosis

The outbreak of shigellosis, caused by a gram negative enteric pathogen-Shigella sonnei, has become a serious issue worldwide. IpgB1 is one of the major proteins involved in type III secretary pathway of the bacteria which mimics the role of Rho-G in membrane ruffling and the simulation of Rac-1. This condition leads to shigellosis and IpgB1 act as a key virulent factor. The infection usually treated by antibiotics; however, most of the strains acquired multiple drug resistance. Hence, there is a demand for alternative therapeutic agents. Computer aided screening is a modern approach to design next generation medicines. But the 3D structure of the protein is not available in native form which is essential for structure based drug designing. Hence, a 3D model of IpgB1 was generated by homology modeling. The model was refined and validated by various bioinformatics tools. The Ramachandran plot of the model accounts for 92.9% of the modeled residues are in allowed region. The model was used as a probable drug target and the inhibitory properties of selected ligands were studied by molecular docking. The binding efficiencies of known drugs were compared against selected herbal compounds. Herbal leads such as Andrographolide, Cryptolepine and Esculetin (docking binding energy -8.15 kcal/mol, -7.15kcal/mol and -6.79 kcal/mol respectively) were identified as the best inhibitors with minimum binding energies and good pharmacological properties than known chemotherapeutic agents. Present study finds significant application to design novel therapeutics against IpgB1mediated shigellosis