Background: This study aims to identify potential antifungal phytocompounds targeting the spore coat protein COT H3 from Rhizopus, a critical virulence factor in mucormycosis. Mucormycosis, caused by Rhizopus species, is a rapidly progressing and often fatal fungal infection with limited treatment options. COT H3 plays a key role in immune evasion, making it an ideal target for antifungal therapy. The objective is to discover compounds that inhibit COT H3, offering a novel therapeutic strategy.
Materials and Methods: A comprehensive in-silico approach was employed, utilizing protein modeling, molecular docking, molecular dynamics (MD) simulations, and binding free energy calculations to screen antifungal phytocompounds. The top compound, Emodin was subjected to ADME (absorption, distribution, metabolism, and excretion) and toxicity analyses to evaluate its drug-like properties and safety.
Results: Emodin demonstrated the highest glide score (-8.37 kcal/mol) and binding free energy (-33.735 kcal/mol). Strong interactions were observed with key residues, including Thr573, Asn571, and Ser408. MD simulations confirmed the stability of the emodin-COT H3 complex. ADME and toxicity analyses showed favorable drug-like properties for emodin.
Conclusion: Emodin exhibits strong potential as an antifungal agent against mucormycosis by inhibiting COT H3. These findings highlight emodin as a promising lead for novel antifungal therapies, improving treatment options for this serious infection.
Keywords: Rhizopus arrhizus, Mucormycosis, Cot H3, COVID-19, Phyto-chemical compounds.
