What are NS5A inhibitors?
What are NS5A inhibitors? Non-structural protein 5A (NS5A) inhibitors are a direct-acting antiviral agent used to treat hepatitis C virus (HCV). The NS5A protein has a substantial role in viral replication, packaging, assembly and complex interactions with cellular functions.
What is NS5A treatment?
NS5A inhibitors are antiviral drugs. They are classified as direct acting agents (DAAs) and work by inhibiting the HCV NS5A protein.
What does NS5A stand for?
Nonstructural protein 5A (NS5A) is a zinc-binding and proline-rich hydrophilic phosphoprotein that plays a key role in Hepatitis C virus RNA replication. It appears to be a dimeric form without trans-membrane helices.
What is NS5A and NS5B?
The hepatitis C virus (HCV) NS5B protein contains the RNA dependent RNA polymerase (RdRp) activity that catalyzes the synthesis of the viral genome with other host and viral factors. NS5A is an HCV-encoded protein previously shown to localize to the replisome and be necessary for viral replication.
What are DAA drugs?
Direct-acting antivirals (DAAs) are a newer class of drugs used to treat hepatitis C. DAAs target specific steps in the hepatitis C virus (HCV) life cycle. DAAs have shorter treatment times, fewer side effects, and higher SVR rates than older drugs.
What is a non nucleoside polymerase inhibitor?
Non-nucleoside polymerase inhibitors Non-nucleoside inhibitors bind outside the active site and target allosteric sites on the surface of the enzyme, downregulating the RdRp activity through induction of conformational changes (Fig. 1). Non-nucleoside inhibitors are so far specific for HCV genotype 1.
What is NS5A testing?
The HCV NS5A Drug Resistance Assay is a genotypic (sequencing) resistance assay that analyzes the nonstructural (NS) 5A region of hepatitis C virus (HCV) genotypes 1a or 1b using next-generation sequencing (NGS) techniques.
What is Rav testing?
HCV Resistance Testing (RAV testing) Resistance Associated Variants (RAVs) refer to mutations that occur in the target enzymes that confer resistance to DAAs. RAV testing is done in most patients who have failed a prior DAA-containing regimen before they initiate re-treatment with another DAA regimen.
What is non nucleoside polymerase inhibitor?
Non-nucleoside polymerase inhibitors Non-nucleoside inhibitors bind outside the active site and target allosteric sites on the surface of the enzyme, downregulating the RdRp activity through induction of conformational changes (Fig. 1).
Is Sofosbuvir a DAA?
One of the most potent DAA medications is sofosbuvir, a pan-genotypic nucleotide analogue that inhibits the NS5B polymerase of HCV. Daclatasvir, a pan-genotypic inhibitor of the HCV NS5A replication complex, was recently approved in the United States for treatment of HCV genotype 3 in conjunction with sofosbuvir.
Is Epclusa a DAA?
How Many DAA Per Tablet?…Classification of Direct-Acting Antiviral Agents in HCV Treatment Regimens Hepatitis C.
| DAA Trade Name | DAA Generic Name | Abbreviation |
|---|---|---|
| Epclusa® | sofosbuvir/velpatasvir | SOF/VEL |
| VoseviTM | sofosbuvir/velpatasvir/voxilaprevir | SOF/VEL/VOX |
| MavyretTM | glecaprevir/pibrentasvir | GLE/PIB |
What is the target of the HCV drug Sofosbuvir?
Sofosbuvir is nucleotide analog inhibitor, which specifically inhibits HCV NS5B (non-structural protein 5B) RNA-dependent RNA polymerase.
Is the barrier to resistance for NS5A inhibitors high?
NS5A inhibitors are potent and have pangenotypic coverage (Table 5.2 ). The barrier to resistance of first-generation molecules is low for HCV subtype 1a, high for other genotypes/subtypes ( Brown et al., 2010; Gao et al., 2010; Lawitz, Gruener, et al., 2011; Nettles et al., 2008, 2010; Wang et al., 2012 ).
Are there any second generation NS5A inhibitors available?
Second-generation NS5A inhibitors with improved barrier to resistance will soon reach early clinical development. Daclatasvir, a pangenotypic NS5A inhibitor, is approved in the European Union (2014) for use as part of HCV combination therapy and in the USA (2015) for use specifically with sofosbuvir for treatment of HCV genotype 3.
What is the role of NS5A in HCV replication?
Although it lacks any known enzymatic activities, the viral protein NS5A is required for HCV replication, modulates the cellular immune response, and alters the membranous environment via unknown mechanisms.
Are there any direct acting HCC inhibitors that are NS5A inhibitors?
Direct-Acting HCV Antivirals. Currently, FDA-approved DAAs for combination treatment of CHC include protease inhibitors (simeprevir, paritaprevir, and grazoprevir); polymerase inhibitors (sofosbuvir and dasabuvir); and NS5A inhibitors (ledipasvir, ombitasvir, daclatasvir, velapatasvir, and elbasvir).