|
| ID |
DDInter626 |
| Drug Type |
small molecule |
| Molecular Formula |
C49H55N9O7 |
| Molecular Weight |
882.035
|
| Description |
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.
|
| ATC Classification |
J05AP54
J05AP10
|
| IUPAC Name |
Methyl N-[(2S)-1-[(2S)-2-{5-[(9S)-14-{2-[(2S)-1-[(2S)-2-[(Methoxycarbonyl)Amino]-3-Methylbutanoyl]Pyrrolidin-2-Yl]-1H-Imidazol-5 |
| InChI |
Inchi=1S/C49H55N9O7/C1-27(2)41(54-48(61)63-5)45(59)56-20-10-14-37(56)43-50-25-34(52-43)30-17-19-36-32(22-30)23-39-33-18-16-31(24-40(33)65-47(58(36)39)29-12-8-7-9-13-29)35-26-51-44(53-35)38-15-11-21-57(38)46(60)42(28(3)4)55-49(62)64-6/H7-9,12-13,16-19,22-28,37-38,41-42,47H,10-11,14-15,20-21H2,1-6H3,(H,50,52)(H,51,53)(H,54,61)(H,55,62)/T37-,38-,41-,42-,47-/M0/S1 |
| InChI Key |
BVAZQCUMNICBAQ-PZHYSIFUSA-N |
| Canonical SMILES |
[H][C@]1(CCCN1C(=O)[C@@H](NC(=O)OC)C(C)C)C1=NC=C(N1)C1=CC2=C(C=C1)N1[C@@H](OC3=C(C=CC(=C3)C3=CN=C(N3)[C@]3([H])CCCN3C(=O)[C@@H](NC(=O)OC)C(C)C)C1=C2)C1=CC=CC=C1 |
| Useful Links |
DrugBank
ChEMBL
|