In silico identification of a phosphate marine steroid from Indonesian marine compounds as a potential inhibitor of phosphatidylinositol mannosyltransferase (PimA) in Mycobacterium tuberculosis.

A higher death rate is associated with multiple factors, including medication resistance and co-infection with the human immunodeficiency virus (HIV). This shows the need to obtain new and effective drug candidates in improving tuberculosis (TB) treatment. In addition, the phosphatidylinositol mannosyltransferase (PimA) enzyme starts the production of phosphatidyl-myo-inositol. PimA has been identified as a key enzyme and an important area for further research in the development of anti-TB drugs. Previous research investigated various applications including marine resources driven by a deeper understanding of the distinctive features of the ecosystem and the diverse array of organisms. Therefore, this research aims to investigate the potential of Indonesian marine compounds as inhibitors of PimA, with a focus on binding energy, interaction modes, and stability using docking and molecular dynamics (MD) investigation methodologies. The results show that a total of 84 Indonesian marine compounds are effectively docked to the PimA to obtain compounds 21, 27, and 33 for further investigation. Based on the MD analysis, compound 27 (desulfohaplosamate) is the most promising candidate among the new MTB-PimA inhibitors. Compounds bind to PimA, as shown by a strong affinity of -30.09 kJ/mol, and form hydrogen bonds with the key amino acid residue Gly16. Furthermore, a stable complex is formed to easily analyze the antibacterial agents targeting MTB in the future.