Table 2.

Table showing the mechanism of action of DAAs[52,53,54]

Class of direct antiviral agents	Examples	Mechanism of action	Comments
NS3/4A protease inhibitors	1st generation: Telaprevir, Boceprevir 2nd generation: Simeprevir Next generation drugs: Glecaprevir, Grazoprevir, Paritaprevir, Voxilaprevir	Bind to the active site of the NS3/4A protease	High potency (varies by HCV genotype) Low barrier to resistance (1a<1b) High potential for drug interactions Can cause rash, anemia, and raised bilirubin Later generation drugs like Glecapravir & Grazoprevir are pangenotypic and are expected to have higher barriers to resistance.
NS5A inhibitors	Daclatasvir, Elbasvir, Ledipasvir, Ombitasvir, Pibrentasvir, Velpatasvir	Interact with domain 1 of the NS5A dimer, although the exact mechanism remains to be fully elucidated	Moderate to high potency (consistent across HCV genotypes & subtypes) High barrier to resistance (1a=1b) Low potential for drug interactions; may interact with HIV antiretrovirals (nucleoside reverse transcriptase inhibitors) and ribavirin Can cause mitochondrial toxicity
Nucleos(t) ide analog NS5B polymerase inhibitors	Sofosbuvir	These are incorporated into the nascent RNA chain and result in chain termination by compromising the binding of the next incoming nucleotide	Potency varies by HCV genotype Very low barrier to resistance (1a<1b) Variable potential for drug interactions
Non-nucleoside NS5B polymerase inhibitors	Dasabuvir	Interact with thumb 1, thumb 2, palm 1 or palm 2 domain of NS5B and inhibit polymerase activity by allosteric mechanisms of action	High potency (against multiple HCV genotypes) Low barrier to resistance (1a<1b) Low to moderate potential for drug interactions