A mastoparan-derived peptide has broad-spectrum antiviral activity against enveloped viruses

Abstract

Broad-spectrum antiviral drugs are urgently needed to treat individuals infected with new and re-emerging viruses, or with viruses that have developed resistance to antiviral therapies. Mammalian natural host defense peptides (mNHP) are short, usually cationic, peptides that have direct antimicrobial activity, and which in some instances activate cell-mediated antiviral immune responses. Although mNHP have potent activity in vitro, efficacy trials in vivo of exogenously provided mNHP have been largely disappointing, and no mNHP are currently licensed for human use. Mastoparan is an invertebrate host defense peptide that penetrates lipid bilayers, and we reasoned that a mastoparan analog might interact with the lipid component of virus membranes and thereby reduce infectivity of enveloped viruses. Our objective was to determine whether mastoparan-derived peptide MP7-NH2 could inactivate viruses of multiple types, and whether it could stimulate cell-mediated antiviral activity. We found that MP7-NH2 potently inactivated a range of enveloped viruses. Consistent with our proposed mechanism of action, MP7-NH2 was not efficacious against a non-enveloped virus. Pre-treatment of cells with MP7-NH2 did not reduce the amount of virus recovered after infection, which suggested that the primary mechanism of action in vitro was direct inactivation of virus by MP7-NH2. These results demonstrate for the first time that a mastoparan derivative has broad-spectrum antiviral activity in vitro and suggest that further investigation of the antiviral properties of mastoparan peptides in vivo is warranted.

Sequence-activity relationship, and mechanism of action of mastoparan analogues against extended-drug resistant Acinetobacter baumannii

“…The mastoparan family is a very promising group of potential new drugs. In addition to antiviral activity [35] our results show that mastoparan and some of its analogues may be potential antibacterial agents to treat infections caused by multi-, extended-and pan-drug resistant A. baumannii which have the ability to overcome all the antibiotics administered. Their good in vitro activity against this microorganism allows very high stability in human serum and moderate toxicity in HeLa cells.…”

Antiviral peptides as promising therapeutic drugs

“…In pre-incubation, in vivo assays performed with Indian vesicular stomatitis virus (VSV) and MP7-NH2; the peptide made the virus non-infectious and unable to replicate in vivo. In a transmission electron microscopy (TEM) assay, it was observed that VSV virions treated with mastoparan 7 had a significant envelope disruption, appearing to be separated from the capsid [75].…”

Antiviral activity of animal venom peptides and related compounds

“…Mastoparan-7, a mastoparan analogue, displayed a wide spectrum of antiviral activity against enveloped viruses of five different families (Rhabdoviridae, Poxviridae, Flaviridae, Paramyxoviridae and Herpesviridae) in in vitro assays ( Table 2). Structural studies have indicated pore formation by the insertion of the mastoporan amphiphilic α helix into the viral lipidic envelope, causing its disruption [74].…”