Repurposing antiviral agents against mucormycosis.

Area of Science:

• Mycology
• Infectious Diseases
• Pharmacology

Background:

• Mucormycosis is a severe fungal infection with high mortality, particularly in immunocompromised patients.
• Limited therapeutic options necessitate the development of novel treatment strategies.

Purpose of the Study:

• To identify novel antifungal agents or compounds that enhance amphotericin B (AmB) efficacy against mucormycosis.
• To explore the potential of repurposing antiviral drugs for mucormycosis treatment.

Main Methods:

• Screened 618 antiviral compounds against Rhizopus delemar.
• Conducted time-kill assays and determined drug synergy using fractional inhibitory concentration index (FICI).
• Assessed cytotoxicity against Vero cells to evaluate safety margins.

Main Results:

• Four compounds (IMB-301, U18666A, BLT-1, obefazimod) exhibited potent in vitro antifungal activity.
• Hepatitis C antivirals daclatasvir (DAC) and velpatasvir (VEL) showed significant synergy with AmB, reducing AmB MICs by 4- to 32-fold.
• Combinations demonstrated favorable safety profiles with high selectivity indices (8 to >32).

Conclusions:

• Antiviral repurposing is a viable strategy for developing new mucormycosis treatments.
• DAC and VEL in combination with AmB offer a promising, safer therapeutic approach.
• Further translational research is warranted to advance these findings into clinical practice.