Table 1.
Classes and Characteristics of Direct-Acting Antivirals
| Class | Structural, functional characteristics | Potency | Genetic barrier to resistance | Compound | Current status |
|---|---|---|---|---|---|
| NS3/4A protease inhibitors | |||||
| First-generation | Inhibiting proteolytic maturation of HCV polyprotein | High in G1 | Low to medium | Boceprevir | Approved |
| Covalent linear inhibitors | Low in G2/3 | Telaprevir | Approved | ||
| Noncovalent linear inhibitors | Simeprevir (TMC-435) | Approved | |||
| Macrocyclic inhibitors | Faldaprevir (BI201335) | Phase III | |||
| Asunaprevir (BMC-650032) | Phase III | ||||
| Danoprevir (RG7227) | Phase II | ||||
| Vaniprevir (MK-7009) | Phase III | ||||
| Second-generation | High in all G | Medium | MK-5172 | Phase II | |
| ACH-2684 | Phase II | ||||
| NS5A inhibitors | Biding to domain I of NS5A, resulting in the suppression of RNA synthesis | High | Low to medium | Daclatasvir | Phase III |
| GS-5885 | Phase III | ||||
| ABT-267 | Phase III | ||||
| PPI-668 | Phase II | ||||
| NS5B polymerase inhibitors | |||||
| Nucleos(t)ide inhibitors | Mimics of natural polymerase substrates. Incoporated in the RNA leading to chain termination | High in all G | Medium to high | Sofosbuvir | Approved |
| Mericitabine (RG7128) | Phase II | ||||
| VX-135 | Phase II | ||||
| Nonnucleos(t)ide inhibitors | Binding to the surface of NS5B enzyme | Medium to | Low | ABT-333 | Phase III |
| High | BI207127 | Phase III | |||
| ABT-072 | Phase II | ||||
HCV, hepatitis C virus.