Phytocompounds as potential inhibitors of mycobacterial multidrug efflux pump Rv1258c: an in silico approach

The number of infections and deaths caused by multidrug resistant (MDR) tuberculosis is increasing globally. One of the efflux pumps, that makes Mycobacterium tuberculosis resistant to a number of antibiotics and results in unfavourable treatment results is Tap or Rv1258c. In our study, we tried to utilize a rational drug design technique using in silico approach to look for an efficient and secure efflux pump inhibitor (EPI) against Rv1258c. The structure of Rv1258c was built using the homology modeling tool MODELLER 9.24. 210 phytocompounds were used for blind and site-specific ligand docking against the modelled structure of Rv1258c using AutoDock Vina software. The best docked plant compounds were further analysed for druglikeness and toxicity. In addition to having excellent docking scores, two plant compounds—ellagic acid and baicalein—also exhibited highly desirable drug-like qualities. These substances outperform more well-known EPIs like piperine and verapamil in terms of effectiveness. This data shows that these two compounds might be further investigated for their potential as Rv1258c inhibitors. Key points Rv1258c is an important efflux pump which provides multidrug resistance in mycobacteria. The structure of the pump was prepared using homology modeling and docking studies were conducted against a number of phytocompounds looking for possible efflux pump inhibitors (EPIs). Based on in silico studies, two phytocompounds ellagic acid and baicalein show desirable properties of being an efficient EPI.