Identification of Mycobacterial RNA Polymerase Inhibitors from the Main Phytochemicals of Nigella sativa: An in silico Study

Shabir Ahmad Mir, Mohammed Alaidarous, Bader Alshehri, Bilal Ahmad Mir, Abdul Aziz Bin Dukhyil, Saeed Banawas, Ahmad Firoz, Suliman A. Alsagaby, Yahya Awaji Madkhali, Sadaf Jahan, Faizan Kashoo, Danish Iqbal, Showkat Ahmad Ganaie, Ranjay Kumar Choudhary, Kamal Shaker Albenasy and Asma Naseem

Background and Objective: Tuberculosis (TB), caused by Mycobacterium tuberculosis, is one of the major global public health concerns. Considering the limitations of the current anti-TB chemotherapy and due to the emergence of drug-resistant M. tuberculosis strains, there is an urgent need to discover and/or develop new drugs against TB. Plants and their extracts have been used in therapeutics since ancient times and their therapeutic importance is being increasingly explored in recent times. In this study, we screened the major phytochemicals of the plant, Nigella sativa for assessing their potential to inhibit the RNA polymerase (RNAp) of M. tuberculosis. Materials and Methods: The screening and binding affinity of the selected phytochemicals with RNAp were investigated through a molecular docking approach and the protein-ligand interactions were analyzed using suitable soft-wares. Results: The study reports that out of the nine selected phytochemicals of N. sativa 3 compounds (α-hederin, Dithymoquinone and Nigellidine) possessed significant docking scores/binding energies for RNAp of M. tuberculosis. The compound α-hederin ranked at the top in inhibiting the RNAp of M. tuberculosis as revealed by its lowest binding energy (-8.9 kcal moL^–1). Conclusion: Our results emphasize that α-hederin and dithymoquinone could be considered for ongoing drug development strategies against tuberculosis. However, further investigations are needed to confirm these findings.

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