Identifying the Novel Inhibitors Against the Mycolic Acid Biosynthesis Pathway Target “mtFabH” of Mycobacterium tuberculosis

• DOI: 10.3389/fmicb.2022.818714
• Publication Date: 2022-05-06T14:25:56Z
• Authors: Niranjan Kumar; Rakesh Srivastava; Raj Kumar Mongre; Chandra Bhushan M...; Amit Kumar; Rosy Khatoon; Atanu Banerjee; Md Ashraf-Uz-Zaman; Harpreet Singh; Andrew M. Lynn; Myeong-Sok Lee; Amresh Prakash
• Keywords: Mycolic acid

Mycolic acids are the key constituents of mycobacterial cell wall, which protect bacteria from antibiotic susceptibility, helping to subvert and escape host immune system. Thus, enzymes involved in regulating biosynthesis mycolic can be explored as potential drug targets kill Mycobacterium tuberculosis (Mtb). Herein, Kyoto Encyclopedia Genes Genomes is used understand fatty acid metabolism signaling pathway integrative computational approach identify novel lead molecules against mtFabH (β-ketoacyl-acyl carrier protein synthase III), regulatory enzyme pathway. The structure-based virtual screening antimycobacterial compounds ChEMBL library results selection 10 molecules. Molecular binding drug-likeness properties compared with inhibitor suggest that only two compounds, ChEMBL414848 (C1) ChEMBL363794 (C2), may However, spatial stability free energy estimation thiolactomycin (TLM) C1 C2 using molecular dynamics simulation, followed by mechanics Poisson–Boltzmann surface area (MM/PBSA) indicate better activity (ΔG = −14.18 kcal/mol) TLM −9.21 −13.50 kcal/mol). compound promising candidate for designing inhibitors therapy Mtb.