The Era of Direct-acting Antivirals Has Begun

The Beginning of the End for HCV?

Marie-Louise Vachon, M.D., M.Sc.; Douglas T. Dieterich, M.D.


Semin Liver Dis. 2011;31(4):399-409. 

In This Article

Nonstructural Protein 5A (NS5A) Replication Complex Inhibitors

Inhibitors of NS5A block viral production at an early stage of assembly. The exact mechanism of action of the NS5A protein is unknown.[35] Without having an enzymatic function, this multifunctional protein is essential for replication and assembly of HCV and has no human homologs.[36,37]


BMS-790052 is the first NS5A inhibitor with proof-of-concept in the clinic. The results of the first placebo-controlled, multiple ascending-dose clinical study evaluate its antiviral activity, resistance profile, pharmacokinetics, safety, and tolerability in 30 patients with chronic HCV infection infected with HCV genotype 1 were recently published.[38] Its pharmacokinetic profile supports once-daily dosing and the drug was well tolerated. Patients received BMS-790052 for 14 days. The mean maximum decline from baseline in HCV RNA ranged from 2.8 to 4.1 log10 IU/mL. Most patients experienced viral rebound during the first 7 days of BMS-790052 monotherapy. Viral breakthroughs were associated with mutations that had been previously found in the NS5A at baseline and at the time of resistance development.[39,40]


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