Insilico studies of therapeutic agents in Phytocompounds obtained from mondoro myristica (African nutmeg) against Mycobacterium tuberculosis

Abstract: The highly adaptive cellular response of Mycobacterium tuberculosis to various antibiotics, combined with the high costs of clinical trials, hamper the development of novel antimicrobial agents with improved efficacy and safety. Subsequently, in silico drug screening methods are increasingly used in drug discovery and development and have proven useful for predicting the pharmacokinetics, toxicities, and targets of prospective new antimicrobial agents. In this investigation, we employed a reverse target fishing approach to identify potential hit targets and explore their interactions between M. tuberculosis and a promising new antituberculosis compound. Two of the four identified targets, Cyp130 and 1SFR, were strongly proposed as optimal drug targets for dormant M. tuberculosis, with Cyp130 exhibiting the highest binding affinity. The metabolic pathways associated with the selected target proteins were compared to previously published molecular mechanisms of Cyp130 in M. tuberculosis, confirming disruptions in the metabolism of proteins, cell wall components, and DNA. We also detailed the specific steps within these pathways that are inhibited and elaborated on the role of Cyp130 against dormant M. tuberculosis. This compound has previously shown promising in vitro safety and good oral bioavailability, both of which were supported by this in silico study. The pharmacokinetic properties and toxicity of the compound were predicted and evaluated using the online tools pkCSM and SwissADME, along with Discovery Studio software, further supporting its safety and bioavailability as an antimycobacterial agent. Keywords: Mycobacterium tuberculosis, phytocompounds, mondoro myristica, ADMET. Title: Insilico studies of therapeutic agents in Phytocompounds obtained from mondoro myristica (African nutmeg) against Mycobacterium tuberculosis Author: Dearsly, Emmanuel Markus; Eze, Kingsley Chijioke; Oshatuyi, Olukayode; Shaibu, Aisha Oiza; Nwosu, Uzoamaka Amararachi; Mmadu, Michael Ezenwa International Journal of Novel Research in Life Sciences ISSN 2394-966X Vol. 12, Issue 2, March 2025 - April 2025 Page No: 23-39 Novelty Journals Website: www.noveltyjournals.com Published Date: 17-March-2025 DOI: https://doi.org/10.5281/zenodo.15039264 Paper Download Link (Source) https://www.noveltyjournals.com/upload/paper/Insilico%20studies%20of%20therapeutic%20agents-17032025-3.pdf