Computational study of phytochemical derived bioactive compounds of Vernonia amygdalina as a potential inhibitor of Topoisomerase IV in pneumonia

Several of the bacteria responsible for pneumonia had become resistant to available antibiotics. According to the WHO, the resistance of Klebsiella pneumonia to Ciprofloxacin is 79.4%, making infections such as pneumonia and several diseases more difficult, if not impossible to treat. The prevalence of antimicrobial resistance is a global problem and among the 10 top global health threats facing humanity. With the projection of 10 million deaths per year by 2050 due to bacterial infections associated with antibiotic resistance according to WHO, there is an urgent need to identify an alternative approach to curb the incessant antimicrobial resistance and a complementary approach is to employ the use of naturally occurring compounds with potent antibacterial activities. We employed structural bioinformatics and theoretical chemistry techniques via molecular docking, and pharmacokinetic study, to identify novel S. pneumoniae topoisomerase IV inhibitors. The stringent molecular docking identified Arg140, Arg81, Glu55, Pro84, Met83, and Asn51, as principal amino acid residues for topoisomerase IV ligand interactions. Ten of the bioactive compounds found in Vernonia amygdalina showed a higher binding energy when compared to the reference compound (Ciprofloxacin). The overall analysis of MD results and binding free energy calculations reveal that Luteolin and 7-O-methylwogonin displayed stable trajectories with acceptable RMSD values and sufficient high negative energies throughout the MD simulation run of 100ns. These identified bioactive compounds in this study can be taken further for in vitro and In vivo studies to examine their efficacy against Pneumonia.