Computational Docking and Virtual Screening of Thymus vulgaris as Potential Inhibitors for Multi-Drug-Resistant Tuberculosis (MDR-TB) Target Proteins

Abstract

MDR-TB is a worldwide problem; according to the World Health Organisation (WHO), TB is the second most infectious killer after COVID-19, even above HIV and AIDS. With rising resistance to current antibiotics and limited solutions, the urgent discovery of new, effective, and affordable antibacterials with low toxicity is imperative to combat MDR-TB strains. Multidrug-Resistant tuberculosis (MDR-TB), caused by mycobacterium tuberculosis, is resistant to ethambutol (EMB), which has been widely ported worldwide. EMB resistance is caused by mutations in the embB gene, which encodes the arabinosylindoylacetylinositol synthase enzyme. The mutations are found in M306L, M3306L + E378A, M306V, and D1024N. Caryophyllene oxide, Bisabolene, and Trans-caryophyllene are essential components of the medicinal plant Thymus vulgaris. Hence, this study will introduce an in silico phytochemical-based approach for discovering novel bacterial agents, exploring the potential of a computational approach in therapeutic discovery. This study focuses on screening all these phytochemicals, Caryophyllene oxide, Bisabolene, and Trans-Caryophyllene, as a potential drug candidate to combat MDR-TB infection through a molecular docking approach.

Moreover, the interaction of amino acid analysis, in silico pharmacokinetics, compound target prediction, pathway enrichment analysis, and Molecular Dynamics (MD) simulations were conducted for further investigation. Caryophyllene oxide, Bisabolene, and Trans-Caryophyllene also showed a strong binding affinity against these mutations. in silico pharmacokinetic analysis highlights the potency as a drug candidate, showing strong Adsorption, Distribution, Metabolism, and Excretion (ADME) properties in combination with low toxicity.