Preliminary Characterisation of NP339, a Novel Polyarginine Peptide with Broad Antifungal Activity

Vanessa M. S. Duncan, Daniel Smith, Laura Simpson, Emma Lovie, Laura Katvars, Leon Berge, Jennifer Robertson, Shane Smith, Carol Munro, Derry Mercer, Deborah A. O'Neil* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Fungi cause disease in nearly one billion individuals worldwide. Only three classes of antifungal agents are currently available in mainstream clinical use. Emerging and drug resistant fungi, toxicity, and drug–drug interactions compromise their efficacy and applicability. Consequently, new and improved antifungal therapies are urgently needed. In response to that need, we have developed NP339, a 2-kDa polyarginine peptide that is active against pathogenic fungi from the genera Candida, Aspergillus, Cryptococcus, and others. NP339 was designed based on endogenous cationic human defence peptides, which are constituents of the cornerstone of immune defence against pathogenic microbes. NP339 specifically targets the fungal cell membrane through a charge-charge initiated, membrane interaction and therefore possesses a differentiated safety and toxicity profile to existing antifungal classes. NP339 is rapidly fungicidal and does not elicit resistance in target fungi upon extensive passaging in vitro. Preliminary analyses in murine models indicate scope for therapeutic application of NP339 against a range of systemic and mucocutaneous fungal infections. Collectively, these data indicate that
NP339 can be developed into a highly differentiated, first-in-class antifungal candidate for poorly served invasive and other serious fungal diseases
Original languageEnglish
JournalAntimicrobial Agents and Chemotherapy
Early online date24 May 2021
DOIs
Publication statusE-pub ahead of print - 24 May 2021

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