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Updated: Nov 4, 2025
Quantifying the Antifungal Activity of Peptides Against Candida albicans
Published on: January 13, 2023
Preliminary Characterization of NP339, a Novel Polyarginine Peptide with Broad Antifungal Activity
Vanessa Duncan1, Daniel Smith1, Laura Simpson1
1NovaBiotics, Ltd., Aberdeen, United Kingdom.
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, and Cryptococcus, as well as others. NP339 was designed based on endogenous cationic human defense peptides, which are constituents of the cornerstone of immune defense 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.
Insights
A novel polyarginine peptide, NP339, shows potent antifungal activity against diverse pathogenic fungi. This new therapy offers a differentiated safety profile and potential to combat drug-resistant fungal infections.
Area of Science:
- Mycology
- Infectious Diseases
- Drug Discovery
Background:
- Fungal infections affect nearly one billion people globally.
- Current antifungal therapies face challenges from drug resistance, toxicity, and drug-drug interactions.
- There is an urgent need for novel antifungal agents.
Purpose of the Study:
- To develop and characterize NP339, a novel polyarginine peptide with broad-spectrum antifungal activity.
- To evaluate the mechanism of action and resistance potential of NP339.
- To assess the therapeutic potential of NP339 in preclinical models.
Main Methods:
- NP339, a 2-kDa polyarginine peptide, was designed based on human defense peptides.
- Antifungal activity was tested against pathogenic fungi including Candida, Aspergillus, and Cryptococcus.
- Mechanism of action was investigated through membrane interaction studies.
- In vitro resistance development was assessed via extensive passaging.
- Efficacy was preliminarily evaluated in murine models of fungal infections.
Main Results:
- NP339 demonstrated potent activity against a range of pathogenic fungi.
- The peptide targets the fungal cell membrane via charge-initiated interaction, suggesting a unique safety profile.
- NP339 exhibited rapid fungicidal activity.
- No resistance was observed in target fungi after extensive in vitro passaging.
- Preliminary murine studies showed promise for treating systemic and mucocutaneous fungal infections.
Conclusions:
- NP339 represents a highly differentiated, first-in-class antifungal candidate.
- Its unique mechanism and lack of resistance development address critical unmet needs in antifungal therapy.
- NP339 holds potential for treating serious and invasive fungal diseases, including those caused by resistant strains.
