Tian, X.; Ma, W.; Yusuf, B.; Su, B.; Hu, J.; Zhang, T. Assessment of the Efficacy of the Antihistamine Drug Rupatadine Used Alone or in Combination against Mycobacteria. Pharmaceutics2024, 16, 1049.
Tian, X.; Ma, W.; Yusuf, B.; Su, B.; Hu, J.; Zhang, T. Assessment of the Efficacy of the Antihistamine Drug Rupatadine Used Alone or in Combination against Mycobacteria. Pharmaceutics 2024, 16, 1049.
Tian, X.; Ma, W.; Yusuf, B.; Su, B.; Hu, J.; Zhang, T. Assessment of the Efficacy of the Antihistamine Drug Rupatadine Used Alone or in Combination against Mycobacteria. Pharmaceutics2024, 16, 1049.
Tian, X.; Ma, W.; Yusuf, B.; Su, B.; Hu, J.; Zhang, T. Assessment of the Efficacy of the Antihistamine Drug Rupatadine Used Alone or in Combination against Mycobacteria. Pharmaceutics 2024, 16, 1049.
Abstract
The emergence of drug-resistant mycobacteria has rendered many clinical drugs and regimens ineffective, imposing significant economic and healthcare burden on individuals and society. Repurposing drugs intended for treating other diseases is a time-saving, cost-effective, and efficient approach for identifying excellent anti-mycobacterial candidates or lead compounds. This study is the first to demonstrate that rupatadine (RTD), a drug used to treat allergic rhinitis, possesses excellent activity against mycobacteria without detectable resistance, particularly Mycobacterium tuberculosis and Mycobacterium marinum, with a minimal inhibitory concentration as low as 3.13 µg/mL. Furthermore, RTD exhibited moderate activity against nonreplicating M. tuberculosis with the minimal inhibitory concentrations lower than drugs targeting the cell wall, suggesting that RTD has the great potential to be modified and used for the treatment of nonreplicating M. tuberculosis. Additionally, RTD exhibits partial synergistic effects when combined with clofazimine, pretomanid, and TB47 against M. tuberculosis, providing the theoretical foundation for the development of treatment regimens. Transcriptomic profiling leads us to speculate that eight essential genes may be the targets of RTD or may be closely associated with the mycobacterial resistance to RTD. In summary, RTD may be a promising hit for further anti-mycobacterial drug or regimen optimization, especially in case of nonreplicating mycobacteria.
Keywords
Mycobacteria; Drug resistance; Rupatadine; Drug repurposing; Nonreplicating
Subject
Medicine and Pharmacology, Medicine and Pharmacology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
