Mell How do NS5A inhibitors work?
NS5A inhibitor’s supposed mechanism of action. The inhibitor binds to NS5A domain 1 and prevents RNA from binding, therefore disrupting RNA replication.
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 is HCV protein?
Abstract. The Human Papillomavirus (HPV) E6 protein is one of three oncoproteins encoded by the virus. It has long been recognized as a potent oncogene and is intimately associated with the events that result in the malignant conversion of virally infected cells.
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 NS5A treatment?
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 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.
Is HCV a RNA virus?
HCV is a small enveloped RNA virus belonging to the family Flaviviridae and genus hepacivirus. HCV genomic RNA was single-stranded with positive polarity, which was packaged by core protein and enveloped by a lipid bilayer containing two viral glycoproteins (E1 and E2) to form the virion[24].
Why does hep C treatment fail?
In some cases treatment failure can occur because of relapse. That happens when HCV viral load first falls to an undetectable level during a course of treatment; later, once a course of treatment has ended, HCV subsequently becomes detectable.
What are resistance associated substitutions?
Resistance-associated substitutions (RASs) present at the baseline impair response to DAA due to rapid selection of resistant HCV strains. NS5A is indispensable target of the current DAA treatment regimens.
What are the 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 the role of NS5A in hepatitis C?
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 the role of NS5A in viral replication?
The NS5a protein interacts with other key viral products (NS4B, NS5B, RNA) and host cell proteins (cyclophilin A, kinases, etc.) to regulate viral replication and assembly. The NS5A protein plays a critical role in the formation of endoplasmic reticulum-derived double-membrane vesicles (DMVs), which facilitates efficient viral replication.
What is the structure of the NS5A protein?
Structure. NS5A is derived from a large polyprotein that is translated from the HCV genome, and undergoes post-translation processing by nonstructural protein 3 (NS3) viral protease. Despite no inherent enzymatic activity being attributed to NS5A, its function is mediated through interaction with other nonstructural…
What does the C terminal of NS5A do?
The IFN-sensitivity determining region (ISDR) at the C-terminal of NS5A has been reported to perform strong trans -activating activities, suggesting that NS5A likely functions as a transcriptional activator.