The Plant Defensin Ppdef1 Is a Novel Topical Treatment for Onychomycosis

Nicole L van der Weerden; Kathy Parisi; James A McKenna; Brigitte M Hayes; Peta J Harvey; Pedro Quimbar; Sean R Wevrett; Prem K Veneer; Owen McCorkelle; Shaily Vasa; Rosemary Guarino; Simon Poon; Yolanda M Gaspar; Michael J Baker; David J Craik; Rob B Turner; Marc B Brown; Mark R Bleackley; Marilyn A Anderson

doi:10.3390/jof9111111

The Plant Defensin Ppdef1 Is a Novel Topical Treatment for Onychomycosis

J Fungi (Basel). 2023 Nov 17;9(11):1111. doi: 10.3390/jof9111111.

Authors

Nicole L van der Weerden^{1

2}, Kathy Parisi^{1

2}, James A McKenna^{1

2}, Brigitte M Hayes^{1

2}, Peta J Harvey³, Pedro Quimbar^{1

2}, Sean R Wevrett⁴, Prem K Veneer^{1

2}, Owen McCorkelle^{1

2}, Shaily Vasa^{1

2}, Rosemary Guarino^{1

2}, Simon Poon^{1

2}, Yolanda M Gaspar^{1

2}, Michael J Baker^{1

2}, David J Craik³, Rob B Turner⁴, Marc B Brown⁴, Mark R Bleackley^{1

2}, Marilyn A Anderson^{1

2}

Affiliations

¹ La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia.
² Hexima Ltd., La Trobe University, Melbourne, VIC 3086, Australia.
³ Institute for Molecular Bioscience, The Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, The University of Queensland, Brisbane, QLD 4072, Australia.
⁴ MedPharm Ltd., Surrey Research Park, Surrey GU2 7AB, UK.

Abstract

Onychomycosis, or fungal nail infection, causes not only pain and discomfort but can also have psychological and social consequences for the patient. Treatment of onychomycosis is complicated by the location of the infection under the nail plate, meaning that antifungal molecules must either penetrate the nail or be applied systemically. Currently, available treatments are limited by their poor nail penetration for topical products or their potential toxicity for systemic products. Plant defensins with potent antifungal activity have the potential to be safe and effective treatments for fungal infections in humans. The cystine-stabilized structure of plant defensins makes them stable to the extremes of pH and temperature as well as digestion by proteases. Here, we describe a novel plant defensin, Ppdef1, as a peptide for the treatment of fungal nail infections. Ppdef1 has potent, fungicidal activity against a range of human fungal pathogens, including Candida spp., Cryptococcus spp., dermatophytes, and non-dermatophytic moulds. In particular, Ppdef1 has excellent activity against dermatophytes that infect skin and nails, including the major etiological agent of onychomycosis Trichophyton rubrum. Ppdef1 also penetrates human nails rapidly and efficiently, making it an excellent candidate for a novel topical treatment of onychomycosis.

Keywords: NMR; Ppdef1; Trichophyton rubrum; antifungal; onychomycosis; plant defensin.

Grants and funding

In addition to their roles at La Trobe University, N.L.v.d.W., K.P., B.M.H., J.A.M., Y.M.G., M.J.B., P.Q., S.P., P.K.V., M.J.B., O.M., S.V., R.G., M.R.B. and M.A.A. were employees of Hexima Ltd. Hexima funded the research described in this manuscript. Work in DJCs lab on peptide structures is supported by the access to the facilities of the ARC Centre of Excellence for Innovations in Peptide and Protein Science (CE200100012) and by an Australian Research Council Laureate Fellowship (FL150100146).