Article
Medicines for Malaria Venture COVID Box: a source for repurposing drugs with antifungal activity against human pathogenic fungi
Registro en:
PAES, Rodrigo de Almeida et al. Medicines for Malaria Venture COVID Box: a source for repurposing drugs with antifungal activity against human pathogenic fungi. Memórias do Instituto Oswaldo Cruz, v. 116, p. 1-10, 2021.
0074-0276
10.1590/0074-02760210207
1678-8060
Autor
Paes, Rodrigo de Almeida
Andrade, Iara Bastos de
Ramos, Mariana Lucy Mesquita
Rodrigues, Marcus Vinícius de Araújo
Nascimento, Vinícius Alves do
Bernardes-Engemann, Andréa Reis
Frases, Susana
Resumen
BACKGROUND: Treatment of mycoses is often ineffective, usually prolonged, and has some side effects. These facts highlight the importance of discovering new molecules to treat fungal infections. OBJECTIVES: To search the Medicines for Malaria Venture COVID Box for drugs with antifungal activity. METHODS: Fourteen human pathogenic fungi were tested against the 160 drugs of this collection at 1.0 µM concentration. We evaluated the ability of the drugs to impair fungal growth, their fungicidal nature, and morphological changes caused to cells. FINDINGS: Thirty-four molecules (21.25%) presented antifungal activity. Seven are antifungal drugs and one is the agricultural fungicide cycloheximide. The other drugs with antifungal activity included antibiotics (n = 3), antimalarials (n = 4), antivirals (n = 2), antiparasitcs (n = 3), antitumor agents (n = 5), nervous system agents (n = 3), immunosuppressants (n = 3), antivomiting (n = 1), antiasthmatic (n = 1), and a genetic disorder agent (n = 1). Several of these drugs inhibited Histoplasma capsulatum and Paracoccidioides brasiliensis growth (15 and 20, respectively), while Fusarium solani was not affected by the drugs tested. Most drugs were fungistatic, but niclosamide presented fungicidal activity against the three dimorphic fungi tested. Cyclosporine affected morphology of Cryptococcus neoformans. MAIN CONCLUSIONS: These drugs represent new alternatives to the development of more accessible and effective therapies to treat human fungal infections.