Molecular Docking and Molecular Dynamics Simulation Study of Anti-Tuberculosis Drug Candidates from Plant-Derived Natural Products against InhA Protein
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Abstract
Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis and is responsible for millions of deaths worldwide every year. Tuberculosis has become a serious public health problem that needs to be eradicated. Current treatments, including first line medication, have unwanted side effects and face the serious problem of multi-drug resistance. Therefore, finding new agents to treat tuberculosis is critically necessary. Thus, in the present study, we aimed to evaluate several plant-derived drug candidates for their anti-tuberculosis activity that work by inhibiting the activity of the Enoyl acyl carrier protein reductase (InhA) enzyme as determined through in silico studies. Drug-likeness and toxicity evaluation, molecular docking, and molecular dynamics simulations were performed to assess new anti-tuberculosis candidates. Plant-derived natural products such as sulcanal, stigmasterol, zambesiacolactone B, coronarin B, zeylenol, galanal B, and galanolactone might have anti-tuberculosis activity according to their binding affinity scores compared to control drugs. The results revealed that sulcanal had the greatest antituberculosis activity by inhibiting InhA compared to other compounds with the most favorable binding affinity score and binding interaction properties. Finally, molecular dynamics simulation demonstrated that sulcanal had constant and stable pattern during the initial to terminal stage of the simulation. Finally, we suggest that sulcanal might have the potential for further development as an anti-tuberculosis drug candidate through its InhA inhibition.
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