Navy

Anti-fungal pharmaceutical compounds

Four naturally occurring peptides have been found to have heightened activity against a wide array of infectious species of fungi

Medical & Biotechnology

Fungal infections are difficult to eradicate and can rapidly evolve into an invasive and systemic disease. These infections require long treatment durations and are associated with high morbidity and mortality, especially in certain populations such as immunocompromised, neonate, and burn patients. Potentially fatal fungal infection cases total over 2 million annually.

Fungi are eukaryotes and thus existing antifungal therapeutics may attack similar molecular targets on mammalian cells, resulting in severe side-effects and dosing limitations. Moreover, the formation of biofilms by pathogenic fungal species may result in a significant decrease in susceptibility to conventional antifungal agents. These challenges are exacerbated by the rise of drug resistance among fungal species, the limited number of clinically approved antifungals, and the low number of new antifungal drugs in the pipeline for pharmaceutical development. Indeed, only three classes of molecules are currently used in clinical practice and only one new class of antifungal drugs has been developed in the last 30 years.

In order to add to the arsenal of antifungals, Navy researchers have developed new pharmaceutical agents from previously identified antibacterial peptides known in the literature as BmKn2, dBmKn2, Kn2-7, and dKn2-7, which were originally isolated from scorpion venom.

Recent research by the Navy has recognized that BmKn2 and Kn2-7 peptides (both “D” and “L” forms) have growth inhibitory, fungicidal, and anti-biofilm activity in in vitro models of Candida albicans infection. It is expected that these peptides, alone or in various combinations will provide effective therapeutics in the fight against both systemic and non-systemic (biofilm and wound) fungal infections.

The peptides are receptive to modification at the N or C terminus, including but not limited to the addition of:

  • targeting ligands such as antibodies to increase cell selectivity and reduce host cell toxicity
  • nanoparticles composed of metallic and non-metallic substances such as gold, silver, polymers, or silica
  • other nonmetal nanoparticles such as dendrimers
  • lipophilic groups such as cholesterol or vitamin E
  • aliphatic acids to increase antifungal activity
  • photosensitizers; and
  • other antifungal antibiotics

The peptides can also be immobilized onto various materials or surfaces, such as collagen matrices, or incorporated into coatings for surfaces or into biomaterials used for tissue matrices, catheters, and other medical or dental implants and devices.

Fungi to be treated with pharmaceutical compositions containing one or more of these peptides include, (but are not limited to), pathogenic species such as: Aspergillus; Blastomyces; Candida; Fusarium; Trichosporon; Penicillium; Coccidioides; Cryptococcus neoformans; Cryptococcus gatlii; Histoplasma; Mucorales; Pneumocystis; Sporothrix; Trichophyton, Microsporum, Epidermophyton, Exserohilum, and Cladosporium.

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