Proteome wide screening for identification of putative drug target gene in Nautella italica and structure-based ligand screening for therapeutic candidates

Abstract

In silico based subtractive genomic approaches were employed to identify the key drug targets for an opportunistic pathogen Nautella italica, a member of the marine Roseobacter clade that causes bleaching disease in the temperate-marine red macro algae, Delisea pulchra. The aim of this study is to propose new active ligands against bleaching disease seen in algae. Using comparative and subtractive genomic approach, a set of 21 proteins were identified as the therapeutic drug target proteins for algal bleaching. This core set of drug targets has been analyzed for network topology using string network analysis and major hub gene identified by CytoHubba was rpoB (DNA directed RNA Polymerase subunit beta). The three-dimensional structure of rpoB was built by comparative modelling and used to perform a virtual screening of Zinc database by DOCK Blaster server. The 50 top scored compounds were screened for toxicity analysis by OSIRIS Data Warrior and ECOSAR tool. Further refinement by autodock program revealed two compounds ZINC49821385 and ZINC97218938 with the best binding energy of -7.07 and -6.79 respectively. These results indicated that 5-(4- isopropylphenyl)furan-2-carboxamide (ZINC ID 49821385) could be one of the potential ligand to treat bleaching disease in algae.