Peptide Inhibitors of Hepatitis C Virus NS3 Protease

Abstract

Hepatitis C virus (HCV) is a highly prevalent virus and one of the major agents of chronic hepatitis. Since HCV NS3 protease is essential for the processing of HCV polyprotein, this protease is a target of choice to control HCV replication. Peptide inhibitors of NS3 were developed by selective amino acid replacement of six leader sequences, corresponding to regions of HCV polyprotein that are cleaved by NS3. The large numbers of potential 14-mer and 16-mer peptide inhibitors thus obtained were tested against NS3 using the fluorescent probe RETS1 and peptide cofactor SVVIVGRIILSGRA from NS4A protein. This afforded several peptide inhibitors with an IC50 of around 2 microM. These peptides may be good leading compounds for the development of peptidomimetics to control HCV replication in the treatment of chronic hepatitis C.

A review of the antiviral activity of cationic antimicrobial peptides

“…2 ). Most studies have examined the effect of AVPs on human immunodeficiency virus (HIV) [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , 73 peptides demonstrated antiviral activity against HIV, 47 peptides were active against herpes viruses [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , 27 peptides active against hepatitis C virus (HCV) [54] , [55] , [56] , [57] , [58] , [59] , 11 were active against human coronaviruses [39] , [52] , [53] , [60] , [61] , [62] , [63] , [64] , [65] , and 9 showing antiviral activity against the influenza virus [39] , [61] ,…”

“…Scorpion defensin peptide BmKDfsin3 inhibited HCV attachment and subsequent replication by suppressing p38 activation during infection thereby regulating P38 mitogen-activated protein kinase (MAPK) signaling pathway [59] . Ten cationic hydrophobic peptides [54] , [55] targeted a specific region of the HCV polyprotein and prevented NS3 protease activation. All these synthetic peptides showed a net positive charge between +4 to +5, an aliphatic index between 104.62 and 156.92, and a GRAVY score between +0.069 and +0.815.…”

AVPpred: collection and prediction of highly effective antiviral peptides

“…influenza (6–8), HIV (9,10), WNV (11), HCV (12), Rabies (4), HSV (13) and RSV (14), etc. Synthetic analogues of several naturally occurring antimicrobial peptides have been made in an attempt to identify important structural features contributing to the antiviral activity (15).…”

Analysis and Prediction of Highly Effective Antiviral Peptides Based on Random Forests

“…All of the AVPs are derived from either synthetic combinatorial libraries or segments of natural proteins and their homologues. A list of highly effective antiviral peptides against HIV [15], HSV [16], hepatitis C virus [17], influenza virus [18]–[20], rabies virus [21], and west nile virus [22] has been compiled into an online database AVPpred [23]. Recently, there is an dedicated AVP database HIPdb for HIV, comprehensively collecting the experimentally validated HIV inhibiting peptides [24].…”