Hepatitis C virus NS3 protein

Frick DN (2007) The hepatitis C virus NS3 protein a model RNA helicase and potential drug target. Curr Issues Mol Biol 9 1-20... 

Simon B E, Cornell K A, Clark T R, et al. (2003). DNA vaccination protects mice against challenge with Listeria monocytogenes expressing the hepatitis C virus NS3 protein. Infect. Immun. 71 6372-6380. 

Cui, P. Recombinant hepatitis C virus NS3 protein and core antigen for detecting anti-HCV antibodies and sandwich ELISA Kits. PCX Int. Appl. WO 2006081718, 2006 Chem. Abstr. 2006, 145, 229321. 

Tai CL, Chi WK, Chen DS, Hwang LH (1996) The helicase activity associated with hepatitis C virus nonstructural protein 3 (NS3). J Virol 70 8477-8484 Tong X, Chase R, Skelton A, Chen T, Wright-Minogue J, Malcolm BA (2006) Identification and analysis of fitness of resistance mutations against the HCV protease inhibitor SCH 503034. Antiviral Res 70 28-38... 

Li K, Foy E, Ferreon JC et al. Immune evasion by hepatitis C virus NS3/4A protease-mediated cleavage of the Toll-like receptor 3 adaptor protein TRIE Proc Natl Acad Sci USA 2005 102(8) 2992-2997. 

Li XD, Sun L, Seth RB, Pineda G, Chen ZJ (2005) Hepatitis C virus protease NS3/4A cleaves mitochondrial antiviral signaling protein off the mitochondria to evade innate immunity. Proc Natl Acad Sci USA 102 17717-17722... 

One exciting approach is the development of short sequences of RNA that bind specifically to HCV helicase and/or the protease activity found in the same hepatitis C virus-encoded non-structural protein, NS3, and inhibit helicase at sub-micromolar concenttations (Umehara et al. 2005). These molecules could provide the basis for developing potent helicase inhibitors with improved pharmacotherapeutic properties. 

Currently, there is no approved antiviral therapy specifically targeting hepatitis C virus (HCV). The development of an HCV replicon system and our improved understanding of the structure and function of HCV proteins have led to the development of several classes of specific HCV inhibitors. NS3-4A protease inhibitors and NS5B polymerase inhibitors are furthest in development as discussed in Chaps. 2-4 (De and Migliaccio 2005 Manns et al. 2007 Pawlotsky et al. 2007). 

Cicero DO, Barbato G, Koch U, Ingallinella P, Bianchi E, Nandi MC, Steinkuhler C, Cortese R, Matassa V, De Francesco R, Pessi A, Bazzo R, Structural characterization of the interactions of optimized product inhibitors with the N-terminal proteinase domain of the Hepatitis C Virus (HCV) NS3 protein by NMR and modelling studies, J. Mol. Biol., 289 385-396, 1999. 

The protein superfamily of proteases [78, 79], however, is an ideal framework for a directed privileged structure-based masterkey concept. It has already been reported that the 5,5-trans-fused lactam moiety was systematically optimized and explored as a serine protease-directed scaffold by GlaxoSmithKline and has delivered progressible lead compounds for various members of that target class [3], such as thrombin [80, 81], elastase [82, 83], HCMV protease [84, 85], and the hepatitis C virus-encoded NS3-4A protease [86, 87]. Here, the initially identified scaffold was engineered toward the serine protease-wide commonality in substrate binding and processing [3],... 

Bartenschlager, R., Ahlborn-Laake, L., Mous, J., and Jacobsen, H. (1993) Nonstructural protein 3 of the hepatitis C virus encodes a serine-type proteinase required for cleavage at the NS3/4 and NS4/5 junctions. J. Virol. 67,3835-3844. 

P775 peptide, an inhibitor bound to the [C/N] NS3 protein of human hepatitis C virus 10+180 8 24... 

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