Telaprevir | Hepatitis C protease inhibitor

Telaprevir (402957-28-2) is a Hepatitis C NS3/4A protease inhibitor that is in clinical use for genotype 1 infections (IC₅₀ = 354 nM genotype 1b replicon cells; IC₅₀ = 280 nM human fetal hepatocytes infected with genotype 1a HCV-positive patient sera).^1-3 It has been shown to inhibit SARS-CoV2 proteases MPro (IC₅₀ = 15 µM)⁴ and 3CLPro (IC₅₀ = 56 µM)⁵. Telaprevir is also an allosteric inhibitor of DnaK, the bacterial homolog of Hsp70.  It enhanced the efficacy of aminoglycoside antibiotics and reduced resistance to the tuberculosis drug rifampin.⁶

References/Citations:

1. Lin et al. (2006), Discovery and development of VX-950, a novel, covalent, and reversible inhibitor of hepatitis C virus NS3.4A serine protease; Infect. Disord. Drug Targets, 6 3
2. Perni et al. (2006), Preclinical profile of VX-950, a potent, selective, and orally bioavailable inhibitor of hepatitis C virus NS3-4A serine protease; Antimicrob. Agents Chemother., 50 899
3. Lin et al. (2006), VX-950, a novel hepatitis C virus (HCV) NS3-4A protease inhibitor, exhibits potent antiviral activities in HCV replicon cells; Antimicrob. Agents Chemother., 50 1813
4. Baker et al. (2021), A drug repurposing screen identifies hepatitis C antivirals as inhibitors of the SARS-CoV2 main protease; PLoS One, 16 e0245962
5. Oerlemans et al. (2021), Repurposing the HCV NS3-4A protease drug boceprevir as COVID-19 therapeutics; RSC Med. Chem., 12 370
6. Hosfelt et al. (2022), An allosteric inhibitor of bacterial Hsp70 chaperone potentiates antibiotics and mitigates resistance; Cell Chem. Biol., 29 854