IN-SILICO ANALYSIS OF NATURAL ANTIBACTERIAL COMPOUNDS TARGETING THE PROTEASES OF MYCOBACTERIUM TUBERCULOSIS
Dr. Vemula Vani*, Mala Sayeda, Sucheta Banik and Stuti Chaki
ABSTRACT
Tuberculosis, an infectious deadly disease caused by the various species of Mycobacterium especially Mycobacterium tuberculosis, was emerged from East Africa more than three million years ago. Tuberculosis has become a major problem and the treatment of tuberculosis is one of the most severe challenges at the global level. Proteases of M. tuberculosis act as a major drug targets for M. tuberculosis and for bacterial infections. LspA, Proteasome, ClpP1 and ClpP2 are some of the Mycobacterium tuberculosis proteases have been selected as potential drug targets. Tuberculosis is now a days getting resistance towards the conventional drugs and leading to conditions known as multidrug resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB). This situation has terrified the global health community and raised a demand for new antituberculosis drugs and thus, medicinal plants can be used for the treatment of TB. The objectives of this study are to select natural antibacterial compounds from the medicinal plants based on review of literature and to test the effect of these antibacterial compounds targeting the proteases of M. tuberculosis by in-silico methods. Thirty four natural compounds having antibacterial activity were selected based on review of literature. These compounds were screened based on Lipinski Rule of Five. Out of thirty four compounds, thirty three were found to be positive. These thirty three compounds were tested for their affinity against four potential drug targets (4ZJM, 4UOG, 4UOH and 3KRD) of M. tuberculosis. Docking was carried out using iGEMDOCK software. The docked poses were analyzed based on fitness scores. For each protein target, top five compounds showing high fitness scores were selected and their interactions with respective drug targets were analyzed by post screening analysis using Rasmol. This analysis indicated that among the proteases considered for this study, proteasome (3KRD) was found to be the most potential drug target for M. tuberculosis. Daucosterol from Vasaka and Barbaloin from Aloe vera were found to be the most effective drug candidates for the treatment of tuberculosis.
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