Speaker
Description
Tuberculosis is ubiquitous, the 13$^{th}$ underlying cause of death & the second significant communicable disease after Covid-19. Antibiotic resistance is the chief obstruction in the treatment of Mycobacterium tuberculosis. To accomplish prevention from extensively drug-resistant & multi-drug-resistant TB peptides with minor side effects, high potency against Mycobacterium protein tyrosine phosphatase-B (mPTPB) is in demand, which is chosen as a target for our study. mPTPB is pivotal for Mtb intracellular survival, resulting in decreased macrophage apoptotic activity and demolition of an innate immune response, leading to reduced secretion of inflammatory cytokines IL-6. We aim to study detailed docking-based investigations of tripeptides against mPTPB as potent inhibitors with more negative docking scores based on ΔG value compared to standard cefsulodin. Through preliminary drug-like filters of Lipinski rules and Molinspiration, five tripeptides (PRO-ARG-CYS, ARG-CYS-LYS, ARG-CYS-GLY, ARG-CYS-ALA, ARG-CYS-MET) were selected out of 154 tripeptides. Swiss DOCK online tool was used for docking using mPTPB as target (PDB ID: 1C83) with HP Laptop having Intel Core i5 processor with 8GB Ram and 64-bit operating system. Among the results obtained, ARG-CYS-LYS was found to be the most promising lead as a potent mPTPB inhibitor with a ΔG value of -9.08 kcal/mol in comparison to Cefsulodin (ΔG value = -11.54 kcal/mol) followed by ARG-CYS-MET (ΔG value = -9.04 kcal/mol), PRO-ARG-CYS (ΔG value = -8.50 kcal/mol), ARG-CYS-GLY (ΔG value = -8.43 kcal/mol) and ARG-CYS-ALA (ΔG value = -8.33 kcal/mol). These results indicate that ARG-CYS-LYS can be considered an excellent therapeutic agent against mPTPB.