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SMARt751 targets the transcriptional regulator VirS, inhibiting its ability to bind DNA, which in turn enhances the expression of the mymA operon and activates Ethionamide. This activation increases the antimicrobial efficacy of Ethionamide against Mycobacterium tuberculosis, and overcomes its resistance. Furthermore, SMARt751 augments Ethionamide's antibacterial activity in mouse models and reduces its effective dose. Additionally, SMARt751 can permeate the blood-brain barrier.