The general aim of the present proposal is to evaluate the effectiveness and mechanism of action of antimicrobial peptides (AMPs) derived from frog-skin secretion on different DNA and RNA enveloped viruses.
The emergence of drug-resistant strains and the lack of specific therapies to prevent or treat emerging viruses whose pathogenesis is still obscure, make the search for new antiviral agents always needful. Temporins are a family of AMPs derived from frog-skin secretion. There are many evidences about their antibacterial/antifungal properties, while very little is known about their efficacy against viruses. We have recently demonstrated that Temporin B (TB) is able to significantly inhibit herpes simplex virus type 1 (HSV-1) replication. Particularly, TB exerts a strong antivirucidal activity against HSV-1. In fact, transmission electron microscopy analysis has shown that incubation of TB with the virus alone causes partial degradation of viral envelope. However, its mechanism of action remains to be elucidated. Due to the fact that TB seems to be a promising antiviral agent against an enveloped virus, our attention will be devoted to the evaluation of these peptides on other enveloped viruses.
In detail, the specific aims of the present proposal will be: a) to evaluate the potential antiviral activity of temporins on different enveloped viruses; b) to deepen TB activity on HSV-1 replication and c) to test the effect of other AMPs (bombinin H family) on HSV-1.
To achieve these objectives the following tasks will be performed:
1) Evaluation of antiviral activity of temporins on HSV-2, influenza, parainfluenza and zika viruses;
2) Characterization of TB virucidal activity on HSV-1;
3) Evaluation of potential antiviral activity of bombinins H2 and H4 on HSV-1 replication.
Nowadays, very little is known about the antiviral activity of AMPs derived from frog-skin secretion, particularly few data are present in literature on temporins or bombinins H efficacy. Thus, results obtained from the present proposal will contribute to expand knowledge for their potential use and to deepen their mechanism of action. Furthermore, our data will allow finding natural peptides effective against enveloped viruses. These peptides may be administered to strains resistant to conventional drugs and considered a further weapon for the emerging viruses, like zika, whose therapy is still limited or not approved.