What is a NS5A inhibitor?
What is a NS5A inhibitor?
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 nucleotide polymerase inhibitor?
Nucleoside/nucleotide analogue polymerase inhibitors (NPIs) are analogues of natural substrates that bind the active site of NS5B and terminate viral RNA chain generation and generally provide a high genetic barrier to resistance and are effective in all genotypes.
What is NS5A treatment?
Ledipasvir/sofosbuvir (Harvoni) Ledipasvir inhibits HCV NS5A protein, which is required for viral replication. Sofosbuvir is an inhibitor of HCV NS5B RNA-dependent polymerase. The oral combination is indicated for treatment of adults with chronic hepatitis C infection with genotype 1, 4, 5, or 6.
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.
How do NS3/4A protease inhibitors work?
The NS3/4A protease interferes with the pathogen recognition TLR3- and RIG-I/MDA5-mediated signaling pathways, by cleaving TRIF and MAVS (also known as Cardif, VISA or IPS-1) signaling adaptors, respectively, preventing the transcriptional activation of type I interferon (IFN) genes and IFN-stimulated genes (ISGs) [2].
How do NS5B inhibitors work?
In contrast to the nucleoside inhibitors, non-nucleoside analogue inhibitors do not compete with nucleotides nor the RNA template. Instead, by binding to RNA-dependent RNA polymerase, they inhibit polymerase activity by inhibiting conformational changes which are necessary for NS5B activity.
Is interferon a NS5A inhibitor?
Hepatitis C virus NS5A protein inhibits interferon antiviral activity, but the effects do not correlate with clinical response.
What is the antiviral drug ribavirin?
Ribavirin, also known as tribavirin, is an antiviral medication used to treat RSV infection, hepatitis C and some viral hemorrhagic fevers. For hepatitis C, it is used in combination with other medications such as simeprevir, sofosbuvir, peginterferon alfa-2b or peginterferon alfa-2a.
Is NS5A an enzyme?
While no known enzymatic function has been ascribed to NS5A, it is an essential component of the HCV replicase and exerts a wide range of effects on cellular pathways and processes, including innate immunity and host cell growth and proliferation.
What is NS3 4A?
The NS3/4A protease is responsible for selective cleavage of polyproteins into individual viral proteins (NS4A, NS4B, NS5A, and NS5B).
Which of the following is a NS3/4A protease inhibitor?
Two NS3-4A protease inhibitors (telaprevir and boceprevir) have been recently approved for the treatment of hepatitis C in combination with standard of care (pegylated interferon plus ribavirin).
What are nonstructural protein 5A ( NS5A ) inhibitors?
Nonstructural protein 5A (NS5A) inhibitors belong to a class of antiviral drugs called protease inhibitors. They are direct acting antiviral agents (DAAs) that target viral proteins, and their development was a culmination of increased understanding of the viral life cycle. However, their mechanism of action is complex and not fully understood.
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.
Where are NS5A inhibitors located in the HCV genome?
The HCV genome. NS5A in the bottom row, second from the right. Nonstructural protein 5A (NS5A) inhibitors belong to a class of antiviral drugs called protease inhibitors. They are direct acting antiviral agents (DAAs) that target viral proteins, and their development was a culmination of increased understanding of the viral life cycle.
Where did the discovery of NS5A come from?
The discovery of NS5A inhibitors took place within the context of a pursuit for a treatment for HCV. NS5A is among the seven nonstructural proteins that form a complex with viral RNA within infected cells to initiate HCV replication.
