Identification of pyrvinium pamoate as an anti-tuberculosis agent and by SOSA approach amongst known drugs.

Tuberculosis (TB), caused by () bacteria, is a leading infectious cause of mortality worldwide. The emergence of drug-resistant has made control of TB more difficult. The selective optimization of side activities (SOSA) approach uses old drugs for new pharmacological targets. In the present study by using SOSA approach, we have successfully identified pyrvinium pamoate (PP) which is capable of inhibiting the growth of mycobacteria, including H37Rv, , Bacille Calmette-Guérin (BCG), H37Ra, and drug-resistant clinical isolates from 1280 known drugs library. The MIC of PP, the minimum inhibitory concentration that inhibits more than 99% of H37Rv and the drug-resistant clinical isolates, ranges from 1.55 to 4.8 µg/mL. Importantly, PP could reduce the bacterial colony-forming units (CFUs) in lung, spleen and liver tissues, and effectively inhibit inflammatory response in H37Rv, multidrug-resistant (MDR) and extensively drug-resistant (XDR) -infected mice. Our results clearly show that the PP has the potential application for treatment of TB.