NS5A

The single-stranded RNA genome of HCV is translated upon entry into the cell into a precursor polyprotein, which is subsequently cleaved into individual proteins. Based on their functions in the viral life cycle, these individual proteins can be divided into 2 groups: structural proteins (C, E1 and E2) and non-structural proteins (p7, NS2, NS3 [protease], NS4A, NS4B, NS5A, NS5B [replicase]).

NS5A is a 447-amino acid protein that plays a critical role in HCV replication, modulation of cellular signaling pathways and interferon response. It contains a putative interferon sensitivity-determining region and appears to be involved in resistance to α interferon. The essential nature of NS5A has been demonstrated in vivo with a single amino acid substitution in the protein.

Genetic studies with different mutants also demonstrated that NS5A is required for HCV subgenomic RNA replication in the cell-based replicon system. As an active component of the viral replication complex, NS5A directly interacts with NS5B replicase, viral RNA and multiple cellular proteins. As a multifunctional protein required for in vivo and in vitro replication, NS5A represents an attractive target for therapeutic intervention (reviewed in Schmitz & Tan, 2008).

Presidio’s NS5A inhibitor program, currently in clinical development, is well positioned to compete in the growing HCV therapy market, based on the overall profile of the compounds in development.

HCV References:
Schmitz U and Seng-Lai Tan. 2008. NS5A – From obscurity to new target for HCV therapy. Recent Patents on Anti-Infective Drug Discovery 3(2): 1-16.

<< Programs & Pipeline