Elbasvir

Elbasvir is a direct-acting antiviral medication used as part of combination therapy to treat chronic hepatitis C, an infectious liver disease caused by infection with hepatitis C virus (HCV). HCV is a single-stranded RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, affecting 72% of all chronic HCV patients.^L852 Treatment options for chronic hepatitis C have advanced significantly since 2011, with the development of direct-acting antivirals (DAAs) such as elbasvir. Elbasvir is an inhibitor of NS5A, a protein essential for viral replication and virion assembly.synthesis The barrier to the development of resistance to NS5A inhibitors is lower than that of NS5B inhibitors, another class of DAAs.^A19593 Substitutions at amino acid positions 28, 30, 31, or 93 are known to confer resistance to elbasvir.^L10253 Despite this disadvantage elbasvir is still effective against HCV, particularly when paired with grazoprevir.

Elbasvir is available as a fixed-dose combination product with grazoprevir (tradename: Zepatier) used for the treatment of chronic hepatitis C. Approved in January 2016 by the FDA, Zepatier is indicated for the treatment of HCV genotypes 1 and 4 with or without ribavirin depending on the presence of resistance-associated amino acid substitutions in the NS5A protein and previous treatment failure with ribavirin, peginterferon alfa-2a, peginterferon alfa-2b, or other NS3/4A inhibitors like boceprevir, simeprevir, or telaprevir.^L10253 Elbasvir and grazoprevir are used with or without ribavirin with the intent to cure, or achieve a sustained virologic response (SVR), and have been shown to achieve a SVR between 94% and 97% for genotype 1 and 97% and 100% for genotype 4 after 12 weeks of treatment.^L852. SVR and eradication of HCV infection are associated with significant long-term health benefits including reduced liver-related damage, improved quality of life, reduced incidence of hepatocellular carcinoma, and reduced all-cause mortality.^A19626

In a computational target-based drug repurposing investigation published in April 2020, elbasvir was predicted to bind stably and preferentially to three proteins necessary for viral replication of SARS-CoV-2, the human coronavirus responsible for the COVID-19 pandemic.^A193257 While these results are suggestive of antiviral efficacy, follow-up clinical trials are required to validate elbasvir as a potential therapy against SARS-CoV-2.