Comparative Genomics Based Putative Drug Targets Identification, Homology Modeling, Virtual Screening and Molecular Docking Studies in Chlamydophila Pneumoniae

R. C. Shivamurthy,1

Ravindranath B S,2*Email

Santhosh K H,3

Murthy BRN1 

Sandeep Nambiar S.1

1Department of Mechanical and Manufacturing Engineering, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal-576104, Karnataka, India.

2*Department of Biotechnology, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal-576104, Karnataka, India.

3Department of Biotechnology and Bioinformatics, Kuvempu University, Shankaraghatta - 577451, Karnataka, India.

Abstract

Chlamydophila pneumoniae is an obligate intracellular Gram-negative human respiratory pathogen acquiring resistance to current antibiotics. Novel strategies including comparative genomics are vital to discover new drug targets to overcome global antibiotic resistance. Current study’s primary objective is to identify the novel drug targets based on patho-genome (synteny) analysis and prioritize the chronic obstructive pulmonary disease (COPD) therapeutic targets. The orthologous syntons based on patho-genomes were compared using SynteView, and classification of orthologous genes based on non-host prediction, essentiality analysis, protein-protein interactions study, toxicity, and druggability analysis were directional in identifying potential drug targets. A total of six hundred and thirty-nine orthologous syntons were identified and classified by prioritizing nrdA and rpoB as potential drug targets. Virtual screening of natural ligands led to the selection of twenty-one ligands, and further ADMET analysis was effective in considering nine ligands. Molecular docking analysis was crucial in analyzing the binding affinity and different binding modes of the nine ligands selected and prioritizing two ligands (CNP0057221 (-6.1 kcal/mol), CNP0372149 (-5 kcal/mol) as potential putative drugs subjected to Molecular dynamics simulation and in vitro based evaluation. The results reported may be vital in novel drug research in the current multi-drug resistance and extensive-drug resistance situation.

Comparative Genomics Based Putative Drug Targets Identification, Homology Modeling, Virtual Screening and Molecular Docking Studies in Chlamydophila Pneumoniae