Consensus scoring-guided virtual screening identifies potent anti-saprolegniasis compounds targeting a P450 fusion...

Area of Science:

• Aquaculture
• Mycology
• Drug Discovery

Background:

• Saprolegniasis, caused by *Saprolegnia* spp., poses a major economic threat to aquaculture.
• The ban on malachite green due to carcinogenicity necessitates new treatments.
• Targeting *Saprolegnia*'s unique cytochrome P450 offers a novel therapeutic strategy.

Purpose of the Study:

• To identify FDA-approved drugs effective against *Saprolegnia* by targeting cytochrome P450.
• To evaluate the *in vitro* anti-saprolegnia activity of selected drug candidates.

Main Methods:

• Virtual screening of FDA-approved drugs using multiple docking tools and consensus scoring.
• Selection of compounds based on P450 inhibition ranking and water solubility.
• *In vitro* testing of selected compounds to determine anti-saprolegnia activity (MIC₅₀).

Main Results:

• Chlorhexidine and diminazene demonstrated significant *in vitro* anti-saprolegnia activity.
• Minimum inhibitory concentration (MIC₅₀) values were 10.93 μg/ml for chlorhexidine and 417 μg/ml for diminazene.
• Chlorhexidine showed substantial inhibition at low concentrations, indicating therapeutic potential.

Conclusions:

• Chlorhexidine and diminazene are promising candidates for aquaculture disease treatment.
• Targeting cytochrome P450 is a viable strategy for developing new anti-saprolegnia agents.
• Further development of chlorhexidine could provide a safer alternative to malachite green.