Identification of potent Antigen 85C inhibitors of Mycobacterium tuberculosis via in-house lichen library and binding free energy studies Part-II

Tuberculosis remains the cause of mortality throughout the world. Currently, the available anti-tubercular drugs are not effective because of the existence of Multi-Drug resistant tuberculosis (MDR-TB) and Extensively-Drug resistant tuberculosis (XDR-TB). It has, therefore, become necessary to develop novel drugs that inhibit the activity of drug-resistant Mycobacterium tuberculosis. Due to the existence of MDR and XDR-TB, Mtb Ag85C has risen out as a propitious molecular drug target as it has importance in the synthesis of main components of the Mtb cell envelope which are essential for the virulence and survival of Mtb. In a previous paper, we studied a potential drug target by virtual high throughput screening of compounds and in continuation of the study on Mtb Ag85C, we further studied the role of lichen compounds in the inhibition of Ag85C. In the current research work, virtual screening of a lichen compounds library was performed against Ag85C. Further, ADMET analysis was employed to filter out the screened lichen compounds. Bioactivity score and toxicity prediction finalized four lichen compounds i.e. Portentol, Aspicilin, Parietinic acid and Polyporic acid as potential inhibitors of Ag85C. The stability and dynamic behavior of four compounds were analyzed by using Molecular dynamics simulation which indicated that they may be potential inhibitors of Ag85C. Therefore, based on the above results, Portentol, Aspicilin, Parietinic acid and Polyporic acid may be potential drug candidates against Mtb. We suggest that the use of these compounds can minimize the treatment time-period and the various side effects associated with the currently available anti-tubercular drugs. [Display omitted] •Existence of drug-resistant tuberculosis is the main failure of currently available anti-tubercular drugs.•Ag85C is a propitious molecular drug target that has importance in the biosynthesis of Mtb cell wall.•Screening and identification of lichen compounds as inhibitors of Ag85C.