Olorofim Effectively Eradicates Dermatophytes In Vitro and In Vivo

    Esmat Mirabzadeh, Atefeh Sharifirad, Nasrin Pashootan, Mahsa Nayebhashemi, Mozhgan Zahmatkesh, Somayeh Enayati, Mehdi Razzaghi‐Abyaneh, Vahid Khalaj
    TLDR Olorofim effectively treats fungal skin infections.
    Olorofim, a new antifungal compound targeting pyrimidine biosynthesis, was tested for its efficacy against dermatophytes both in vitro and in vivo. In vitro tests using microtiter broth dilution showed high sensitivity of dermatophytes to olorofim (MIC = 0.015-0.06 mg/liter). Bioinformatic analysis revealed that the binding site of olorofim on dihydroorotate dehydrogenase (DHODH) is highly conserved among dermatophytes, similar to Aspergillus fumigatus. In vivo tests on guinea pigs infected with Microsporum gypseum demonstrated that daily topical application of olorofim for 1 week resolved skin lesions and restored normal hair growth, comparable to the effects of clotrimazole. These findings suggest that olorofim could be an effective treatment for dermatophytosis.
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