Bedaquiline | Antituberculosis agent/bacterial ATP synthase inhibitor

Bedaquiline (843663-66-1) is a clinically useful antituberculosis agent that is active (MIC’s 0.030 to 0.120 µg/mL) against multi-drug resistant strains.¹ It interferes with mycobacterial energy metabolism via binding to the oligomeric subunit c (AtpE)² and subunit e³ of ATP synthase inhibiting ATP production.⁴ Bedaquiline has recently been found to be an inhibitor (IC₅₀ = 18.7 µM) of the SARS-CoV-2 main protease, 3CLpro.⁵

References/Citations:

1. Andries et al. (2005), A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis; Science, 307 223
2. Koul et al. (2007), Diarylquinolines target subunit c of mycobacterial ATP synthase; Nat. Chem. Biol., 3 323
3. Biukovic et al. (2013), Variations of subunit {varepsilon} of the Mycobacterium tuberculosis F1F0 ATP synthase and a novel model for mechanism of action of the tuberculosis drug TMC207; Antimicrob. Agents Chemother., 57 168
4. Sarathy et al. (2019), Re-Understanding the Mechanisms of Action of the Anti-Mycobacterial Drug Bedaquiline; Antibiotics (Basel), 8 261
5. Ghahremanpour et al. (2020), Identification of 14 Known Drugs as Inhibitors of the Main Protease of SARS-CoV-2; ACS Med. Chem. Lett., 11 2526