A wide range of medium-sized, highly cationic, ?-helical peptides show antiviral activity against herpes simplex virus

Jenssen, Håvard; Andersen, Jeanette H.; Mantzilas, Dimitris; Gutteberg, Tore Jarl

doi:10.1016/j.antiviral.2004.08.003

Cited by 43 publications

(74 citation statements)

References 54 publications

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“…Antiviral compounds not only reduce the number of herpesvirus-induced plaques, they also contribute in the reduction of plaque size (Mikloska and Cunningham, 2001;Jenssen et al, 2004;van der Meulen et al, 2006b). We found that all compounds were able to significantly reduce EHV-1 induced plaque size.…”

Section: Discussionmentioning

confidence: 99%

In vitro susceptibility of six isolates of equine herpesvirus 1 to acyclovir, ganciclovir, cidofovir, adefovir, PMEDAP and foscarnet

Garré

Meulen

Nugent

et al. 2007

Veterinary Microbiology

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Equine herpesvirus 1 (EHV-1) is an important equine pathogen that causes respiratory disease, abortion, neonatal death and paralysis. Although vaccines are available, they are not fully protective and outbreaks of disease may occur in vaccinated herds. Therefore, there is an urgent need for effective antiviral treatment. For three abortigenic (94P247, 97P70 and 99P96) and three neuropathogenic isolates (97P82, 99P136 and 03P37), the effect of acyclovir, ganciclovir, cidofovir, adefovir, 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine (PMEDAP) and foscarnet on plaque number was studied. Additionally, for isolate 97P70, the effect on plaque size was investigated. Ganciclovir was most potent in reducing plaque number, followed by PMEDAP and acyclovir. Adefovir and cidofovir were less effective and foscarnet was the least effective compound. There were no differences detected for acyclovir, ganciclovir, adefovir and PMEDAP between the abortigenic and neuropathogenic isolates. One abortigenic isolate (99P96) was more susceptible to cidofovir and two neuropathogenic isolates (99P136 and 03P37) were less susceptible to foscarnet. For isolate 97P70, all compounds resulted in a significant reduction of plaque size. The most remarkable effect was observed for cidofovir. It was 40-fold more effective in reducing plaque size than in reducing plaque number. In conclusion, ganciclovir was the most potent compound and therefore, may be a valuable candidate for the treatment of EHV-1 infections in horses. The antiviral effect of foscarnet on plaque number was highly dependent on the viral isolate tested. Therefore, it is no valuable antiviral for the treatment of herpesvirus-infections. Cidofovir, although less effective in reducing plaque number, had a strong effect on plaque size. #

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Section: Discussionmentioning

confidence: 99%

In vitro susceptibility of six isolates of equine herpesvirus 1 to acyclovir, ganciclovir, cidofovir, adefovir, PMEDAP and foscarnet

Garré

Meulen

Nugent

et al. 2007

Veterinary Microbiology

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“…For lactoferricin the nature of the aromatic amino acid appeared to be of minor importance for the antiviral activity, although its contribution to the secondary structure and thereby presentation of the charged residues might be crucial (121). Detailed studies on the influence of secondary structure domains on anti-HSV activity illustrated that the ␣-helicity of a peptide could not explain its antiviral activity (122), thus implying that the presentation of the charged residues is of greatest importance with respect to anti-HSV activity (119). This is in accordance with results from Giansanti et al (77) in a study on peptides derived from bovine lactoferrin and hen ovotransferrin.…”

Section: Structural Requirements For Antiviral Peptidesmentioning

confidence: 99%

“…Different strategies for design of such peptides have been pursued. Several groups have looked at the importance of charged and aromatic amino acids, since antiviral peptides are often highly cationic and amphiphilic (45,119,241,269). The hydrophobic character of the peptides has been investigated for a hybrid peptide of cecropin A and magainin-2 (144), while the substitution of D-or L-amino acids has been studied on a set of -defensins (270).…”

Section: Structural Requirements For Antiviral Peptidesmentioning

confidence: 99%

Peptide Antimicrobial Agents

2006

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SUMMARY Antimicrobial host defense peptides are produced by all complex organisms as well as some microbes and have diverse and complex antimicrobial activities. Collectively these peptides demonstrate a broad range of antiviral and antibacterial activities and modes of action, and it is important to distinguish between direct microbicidal and indirect activities against such pathogens. The structural requirements of peptides for antiviral and antibacterial activities are evaluated in light of the diverse set of primary and secondary structures described for host defense peptides. Peptides with antifungal and antiparasitic activities are discussed in less detail, although the broad-spectrum activities of such peptides indicate that they are important host defense molecules. Knowledge regarding the relationship between peptide structure and function as well as their mechanism of action is being applied in the design of antimicrobial peptide variants as potential novel therapeutic agents.

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“…Especially, defensins with a ␤-sheet structure have been gaining much interest because of their antiviral property against HSV (13). Studies of the relationship between structure and function suggested that sequence determinant and secondary structure may be two factors crucial to antiviral activity (32,33). Interestingly, alphadefensins derived from different mammals had only approximately 30% sequence identity (Fig.…”

Section: Figmentioning

confidence: 99%

Enhancement of Antiviral Activity of Human Alpha-Defensin 5 against Herpes Simplex Virus 2 by Arginine Mutagenesis at Adaptive Evolution Sites

Wang

Chen

Wang

et al. 2013

J Virol

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bHerpes simplex virus 2 (HSV-2) infection is still one of the common causes of sexually transmitted diseases worldwide. The prevalence of HSV strains resistant to traditional nucleoside antiviral agents has led to the development of novel antiviral drugs. Human alpha-defensin 5 (HD5), a kind of endogenous antimicrobial peptide expressed in the epithelia of the small intestine and urogenital tract, displays natural antiviral activity. Based on arginine-rich features and adaptive evolution characteristics of vertebrate defensins, we conducted a screen for HD5 derivatives with enhanced anti-HSV-2 activity by a single arginine substitution at the adaptive evolution sites. Cell protection assay and temporal antiviral studies showed that HD5 and its mutants displayed affirmatory but differential anti-HSV-2 effects in vitro by inhibiting viral adhesion and entry. Inspiringly, the E21R-HD5 mutant had significantly higher antiviral activity than natural HD5, which is possibly attributed to the stronger binding affinity of the E21R-HD5 mutant with HSV-2 capsid protein gD, indicating that E21R mutation can increase the anti-HSV-2 potency of HD5. In a mouse model of lethal HSV-2 infection, prophylactic and/or therapeutic treatment with E21R-HD5 via intravaginal instillation remarkably alleviated the symptoms and delayed disease progress and resulted in about a 1.5-fold-higher survival rate than in the HD5 group. Furthermore, the E21R variant exhibited a 2-fold-higher antiviral potency against HIV-1 over parental HD5 in vitro. This study demonstrates that arginine mutagenesis at appropriate evolution sites may significantly enhance the antiviral activity of HD5, which also paves a facile way to search for potent antiviral drugs based on natural antimicrobial peptides.

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A wide range of medium-sized, highly cationic, ?-helical peptides show antiviral activity against herpes simplex virus

Cited by 43 publications

References 54 publications

In vitro susceptibility of six isolates of equine herpesvirus 1 to acyclovir, ganciclovir, cidofovir, adefovir, PMEDAP and foscarnet

In vitro susceptibility of six isolates of equine herpesvirus 1 to acyclovir, ganciclovir, cidofovir, adefovir, PMEDAP and foscarnet

Peptide Antimicrobial Agents

Enhancement of Antiviral Activity of Human Alpha-Defensin 5 against Herpes Simplex Virus 2 by Arginine Mutagenesis at Adaptive Evolution Sites

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