Anti herpes simplex virus activity of lactoferrin/lactoferricin – an example of antiviral activity of antimicrobial protein/peptide

Jenssen, Håvard

doi:10.1007/s00018-005-5228-7

Cited by 92 publications

(58 citation statements)

References 180 publications

(257 reference statements)

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“…We previously reported that cationic ␤-peptides that form a globally amphiphilic helix display antimicrobial activity and that the amphiphilic helix is necessary for activity (44,49). Several studies have demonstrated that cationic antimicrobial peptides have anti-HSV-1 activity and that the antiviral activity requires a globally amphiphilic helical fold (30)(31)(32)(33). Therefore, we expected a cationic ␤-peptide that adopts a globally amphiphilic helix to be active against HSV-1.…”

Section: Discussionmentioning

confidence: 98%

Inhibition of Herpes Simplex Virus Type 1 Infection by Cationic β-Peptides

Akkarawongsa

Potocky²,

English³

et al. 2008

Antimicrob Agents Chemother

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Previously, it was shown that cationic ␣-peptides derived from the human immunodeficiency virus TAT protein transduction domain blocked herpes simplex virus type 1 (HSV-1) entry. We now show that cationic oligomers of ␤-amino acids ("␤-peptides") inhibit HSV-1 infection. Among three cationic ␤-peptides tested, the most effective inhibition was observed for the one with a strong propensity to adopt a helical conformation in which cationic and hydrophobic residues are segregated from one another ("globally amphiphilic helix"). The antiviral effect was not cell type specific. Inhibition of virus infection by the ␤-peptides occurred at the postattachment penetration step, with a 50% effective concentration of 3 M for the most-effective ␤-peptide. The ␤-peptides did not inactivate virions in solution, nor did they induce resistance to infection when cells were pretreated with the ␤-peptides. The ␤-peptides showed little if any toxicity toward Vero cells. These results raise the possibility that cationic ␤-peptides may be useful antiviral agents for HSV-1 and demonstrate the potential of ␤-peptides as novel antiviral drugs.Herpes simplex virus type 1 (HSV-1) is a significant human pathogen causing mucocutaneous lesions primarily in the oral mucosa (cold sores), as well as other sites. More-severe diseases caused by HSV-1 infection include encephalitis, meningitis, and blinding keratitis (65), and HSV-1 is the leading cause of blindness due to infection in developed countries (5). Following an initial infection, HSV-1 establishes latent infection of neurons in sensory ganglia of the host (29), from where it periodically reactivates and causes recurrent lesions at the site of primary infection. To date, none of the currently approved antivirals can eliminate an established latent infection. Because of the difficulties dealing with latency, preventing HSV-1 from entering the cell is an attractive antiviral strategy.HSV-1 entry is a complex process, involving multiple components on both the cell plasma membrane and the viral envelope. The initial interaction involves the binding of viral glycoprotein C (gC) or gB to cell surface heparan sulfate proteoglycan (58). Four viral glycoproteins, gB, gD, and the gH-gL heterodimer, are essential for the subsequent membrane fusion and entry steps (56,57). Following attachment, gD interacts with any of three cellular receptors: herpes virus entry mediator, nectin-1, and 3-O-sulfated heparan sulfate, leading to a conformational change in gD (12,13,21,22,34,39,54,62). This conformational change in gD is believed to trigger the formation of the fusion complex, which is thought to involve the sequential binding of gB to gD, followed by the binding of gH-gL to the gB-gD complex (10,20,23,24,36,41,50,62).

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Section: Discussionmentioning

confidence: 98%

Inhibition of Herpes Simplex Virus Type 1 Infection by Cationic β-Peptides

Akkarawongsa

Potocky²,

English³

et al. 2008

Antimicrob Agents Chemother

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“…Thus, molecules that interfere with the interactions between negatively charged HS chains and their binding partners could represent interesting candidates for the development of pharmacological agents for the treatment of diseases that involve HSPG-protein interactions (33). With regard to HSV infections, in which virus adsorption is mediated by the binding of virion glycoproteins gC and gB to HSPGs (5, 37), natural antimicrobial proteins, such as lactoferrin and its N-terminal pepsin-derived fragment lactoferricin, as well as small chemical antagonists, such as surfen, have been reported to exert antiviral activities via mechanisms of action that involve their binding to HSPGs, thereby blocking HSV entry (14,33). SB105 and SB105_A10 appear to belong to this category of antiviral agents since they are specific for viruses with replication cycles that initiate with the binding of virion proteins to cell surface HPSGs.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Herpes Simplex Virus Type 1 and Type 2 Infections by Peptide-Derivatized Dendrimers

Luganini

Nicoletto

Pizzuto

et al. 2011

Antimicrob Agents Chemother

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In response to the need for new antiviral agents, dendrimer-based molecules have been recognized as having a large number of potential therapeutic applications. They include peptide-derivatized dendrimers, which are hyperbranched synthetic well-defined molecules which consist of a peptidyl branching core and covalently attached surface functional peptides. However, few studies have addressed their applications as direct-acting antiviral agents. Here, we report on the ability of the peptide dendrimer SB105 and its derivative, SB105_A10, to directly inhibit herpes simplex virus 1 (HSV-1) and HSV-2 in vitro replication, with favorable selective indexes discerned for both compounds. An analysis of their mode of action revealed that SB105 and SB105_A10 prevent HSV-1 and HSV-2 attachment to target cells, whereas SB104, a dendrimer with a different amino acid sequence within the functional group and minimal antiviral activity, was ineffective in blocking HSV attachment. Moreover, both SB105 and SB105_A10 retained their ability to inhibit HSV adsorption at pH 3.0 and 4.0 and in the presence of 10% human serum proteins, conditions mimicking the physiological properties of the vagina, a potential therapeutic location for such compounds. The inhibition of HSV adsorption is likely to stem from the ability of SB105_A10 to bind to the glycosaminoglycan moiety of cell surface heparan sulfate proteoglycans, thereby blocking virion attachment to target cells. Finally, when combined with acyclovir in checkerboard experiments SB105_A10 exhibited highly synergistic activity. Taken together, these findings suggest that SB105 and SB105_A10 are promising candidates for the development of novel topical microbicides for the prevention of HSV infections.

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“…The attachment and entry assay results are consistent with haemolymph reducing HSV-1 binding to Vero cells, although at this point we cannot absolutely preclude the possibility that a haemolymph component is internalized simultaneously with the virus to exert its effect on a post-entry event in infection. Antiviral action resembling that described here has been found in the milk protein lactoferrin, its pepsin cleavage product lactoferricin and a number of other highly cationic ahelical peptides, which mediate their activity by binding heparin sulfate on the cellular surface and blocking attachment or entry of HSV-1 (Marchetti et al, 1996;Andersen et al, 2002Andersen et al, , 2004Jenssen et al, 2004a, b;Jenssen, 2005). Prevention of viral entry could also be due to sugar or other compounds with a high affinity for viral attachment/entry glycoproteins competing with cellular receptors, for example chondroitin sulfate type E derived from squid cartilage (Bergefall et al, 2005).…”

Section: ±012mentioning

confidence: 99%

In vitro antiviral activity against herpes simplex virus in the abalone Haliotis laevigata

Vinh

Benkendorff

Speck

2010

Journal of General Virology

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As viruses are extremely abundant in oceans, marine organisms may have evolved novel metabolites to protect themselves from viral infection. This research examined a well-known commercial gastropod, abalone (Haliotidae), which in Australia have recently experienced disease due to a neurotropic infection, abalone viral ganglioneuritis, caused by an abalone herpesvirus (AbHV). Due to the lack of molluscan cell lines for culturing AbHV, the antiviral activity of the abalone Haliotis laevigata was assessed against another neurotropic herpesvirus, herpes simplex virus type 1 (HSV-1), using a plaque assay. The concentration range at which abalone extract was used for antiviral testing caused minimal (,10 %) mortality in Vero cells. Haemolymph (20 %, v/v) and lipophilic extract of the digestive gland (3000 mg ml "1 ) both substantially decreased the number and size of plaques. By adding haemolymph or lipophilic extract at different times during the plaque assay, it was shown that haemolymph inhibited viral infection at an early stage. In contrast, the antiviral effect of the lipophilic extract was greatest when added 1 h after infection, suggesting that it may act at an intracellular stage of infection. These results suggest that abalone have at least two antiviral compounds with different modes of action against viral infection, and provide a novel lead for marine antiviral drug discovery. INTRODUCTIONThe greatest biodiversity on earth is found in oceans, with 32 of the 33 animal phyla, 14 of which are not found on land (Nybakken & Bertness, 2005). Currently there are an estimated 230 000-275 000 taxonomically described marine species, and with the new species inventory accruing 1300-1500 species a year, there is predicted to be between 1.4-1.6 million species of macrofauna and flora in the ocean (Bouchet, 2006). Viruses are also abundant in oceans, with about 10 9 or more viruses per litre of water, exceeding numbers of bacteria and Archaea by about 15-fold (Bergh et al., 1989;Fuhrman, 1999;Suttle, 2007). Viral infections are common in marine environments, with an estimated 10 23 infections occurring every second (Suttle, 2007).Due to natural selection, a range of antiviral agents may have evolved in marine organisms to protect them from viruses. The innate defences available to marine organisms can include secondary metabolites, bioactive peptides and proteins, thus serving as models for the development of new drugs for treating human disease. Indeed, several important antiviral compounds of marine origin have been reported, including didemnins (Caribbean tunicate, Trididemnum solidum), eudistomins (shallow-water tunicates within the genus Eudistoma), mycalamide A and B (New Zealand sponge, Mycale sp.), papuamides A (Theonella mirabilis and Theonella swinhoei sponges), avarone (Dysidea avara sponge), gymnochrome D (fossil crinoid Gymnocrinus richer), microspinosamide (Sidonops microspinosa sponge), solenolide A (gorgonian of the genus Solenopodium), hennoxazole A (Polyfibrospongia sp. sponge), thyrsiferol (red alg...

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Anti herpes simplex virus activity of lactoferrin/lactoferricin – an example of antiviral activity of antimicrobial protein/peptide

Cited by 92 publications

References 180 publications

Inhibition of Herpes Simplex Virus Type 1 Infection by Cationic β-Peptides

Inhibition of Herpes Simplex Virus Type 1 Infection by Cationic β-Peptides

Inhibition of Herpes Simplex Virus Type 1 and Type 2 Infections by Peptide-Derivatized Dendrimers

In vitro antiviral activity against herpes simplex virus in the abalone Haliotis laevigata

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