HCV NS5A Serine Protease

HCV NS5A Serine Protease

HCV is a plus-stranded RNA virus, and its genome with a large open reading frame encodes a poly protein precursor of about 3010 amino acid residues having an internal ribosome entry site at 5` untranslated region (UTR), vital for the translation. This poly protein precursor is cleaved to generate at least 10 proteins, among which the HCV NS3-4A protein. The NS3-4A serine protease is a non-covalent, heterodimer complex formed by two HCV-encoded proteins, the N-terminal serine protease domain of NS3 (catalytic subunit) and the NS4A cofactor (activation subunit). The NS3-4A serine protease is responsible for the proteolytic cleavage at four junctions of the HCV polyprotein precursor: NS3/NS4A (self cleavage), NS4A/NS4B, NS4B/NS5A, and NS5A/NS5B. It is hypothesized that development of a specific inhibitors of NS3 protease activity would be an attractive target for new anti-HCV drugs, since the inhibition of NS3/4A protease will interfere with the viral life cycle and restore the pathways of innate immunity.

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More About HCV NS5A Serine Protease

HCV is a plus-stranded RNA virus, and its genome with a large open reading frame encodes a poly protein precursor of about 3010 amino acid residues having an internal ribosome entry site at 5` untranslated region (UTR), vital for the translation. This poly protein precursor is cleaved to generate at least 10 proteins, among which the HCV NS3-4A protein. The NS3-4A serine protease is a non-covalent, heterodimer complex formed by two HCV-encoded proteins, the N-terminal serine protease domain of NS3 (catalytic subunit) and the NS4A cofactor (activation subunit). The NS3-4A serine protease is responsible for the proteolytic cleavage at four junctions of the HCV polyprotein precursor: NS3/NS4A (self cleavage), NS4A/NS4B, NS4B/NS5A, and NS5A/NS5B[1].  It is hypothesized that development of a specific inhibitors of NS3 protease activity would be an attractive target for new anti-HCV drugs, since the inhibition of NS3/4A protease will interfere with the viral life cycle and restore the pathways of innate immunity[2].

HCV Serine Proteases listed: HCV NS3 Serine Protease, HCV NS4A Serine Protease, HCV NS5A Serine Protease

[1] C. Lin.  HCV NS3-4A Serine Protease. In: S.L. Tan, editor. Hepatitis C Viruses: Genomes and Molecular Biology.Norfolk (UK): Horizon Bioscience; 2006. Chapter 6.
[2] S. Idreess et al. HCV Infection and NS-3 Serine Protease Inhibitors. Virol Mycol 2013, 2, 112.

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