Virucidal activity of human α- and β-defensins against hepatitis C virus genotype 4

Abstract

Hepatitis C virus (HCV) is the major etiological agent of human non-A and non-B hepatitis affecting about 180 million people worldwide. The goal of the current study was to find effective anti-HCV proteins. As a result, defensins were selected as promising candidates due to their well-known anti-viral potential and small size. We conducted in vitro evaluation of two kinds of defensins (human α- and β-defensins and synthetic linear avian α-defensins) using tissue culture combined with reverse transcription nested PCR (RT-nested-PCR) and real-time PCR. Human α- and β-defensins showed strong anti-HCV activity in experiments on cellular protection, neutralization, and treatment at all concentrations used (10, 20 and 50 μg). The synthetic linear defensins could reach similar anti-HCV potential only at a noticeably higher concentration (250 μg) and do not show noticeable activity at 10 and 20 μg. This study suggests that defensins are potent anti-HCV agents.

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] ,…”

“…Peptides P49, P50 and 33 had the lowest IC 50 values of 3 to 3.4 µM ( Table 7 ). A study evaluating the anti-HCV effect of human-alpha, β, and synthetic linear avian alpha-defensins found that human defensins were more active than avian ones, providing cellular protection, neutralization of viruses, and allowing recovery of any HCV-infected cells [57] . Human-alpha and recombinant beta defensins had net positive charges ranging from +2 to +11, aliphatic indexes between 46.11 to 85, and GRAVY scores between -1.008 and +0.55.…”

Antiviral and Immunomodulatory Properties of Antimicrobial Peptides Produced by Human Keratinocytes

“…Interestingly, this effect was higher when combining hBD-2 and hBD-3 than that of the peptides added separately (Quiñones-Mateu et al, 2003;Sun et al, 2005). Finally, hBD-1 to -4, used at 10, 20, and 50 µg/mL, diminished HCV gene expression and cytotoxicity associated with infection in PBMCs and HuH7.5 liver cell line (Mattar et al, 2016b). Conversely, other studies aimed at describing hBD antiviral properties found little or no activity.…”

Inhibitory Activity of a Scorpion Defensin BmKDfsin3 against Hepatitis C Virus

“…Recently, there are many discoveries regarding antiviral defensin polypeptides from scorpions, which may be new candidates for antiviral drug molecules. Human αand β-defensins can suppress HCV replication [35]. Additionally, human α-defensin-1 inhibited protein kinase C (PKC) activation and repressed influenza virus replication [36].…”