Antiretroviral drugs saquinavir and ritonavir reduce inhibitory concentration values of itraconazole against Histoplasma capsulatum strains in vitro

Abstract

Recent studies have shown that some drugs that are not routinely used to treat fungal infections have antifungal activity, such as protease inhibitor antiretroviral drugs. This study investigated the in vitro susceptibility of Histoplasma capsulatum var. capsulatum to saquinavir and ritonavir, and its combination with the antifungal itraconazole. The susceptibility assay was performed according to Clinical and Laboratory Standards Institute guidelines. All strains were inhibited by the protease inhibitor antiretroviral drugs. Saquinavir showed minimum inhibitory concentrations ranging from 0.125 to 1μgmL(-1) for both phases, and ritonavir presented minimum inhibitory concentrations ranging from 0.0312 to 4μgmL(-1)and from 0.0625 to 1μgmL(-1) for filamentous and yeast phase, respectively. Concerning the antifungal itraconazole, the minimum inhibitory concentration values ranged from 0.0019 to 0.125μgmL(-1) and from 0.0039 to 0.0312μgmL(-1) for the filamentous and yeast phase, respectively. The combination of saquinavir or ritonavir with itraconazole was synergistic against H. capsulatum, with a significant reduction in the minimum inhibitory concentrations of both drugs against the strains (p<0.05). These data show an important in vitro synergy between protease inhibitors and itraconazole against the fungus H. capsulatum.

Secreted aspartyl proteinase (PbSap) contributes to the virulence of Paracoccidioides brasiliensis infection

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“…This is not an insignificant question as the yeast and hyphal forms of the dimorphic fungi can have dramatically different susceptibilities. [62][63][64][65][66][67][68][69] For example, early studies with echinocandins showed antifungal effects on the hyphal form of Histoplasma. 67 However, subsequent tests against the yeast form indicated that caspofungin was anywhere from 20-to 1000-fold less effective.…”

Medicines for Malaria Venture COVID Box: a source for repurposing drugs with antifungal activity against human pathogenic fungi

“…Interestingly, the anti- Histoplasma activity of the antivirals saquinavir and ritonavir was previously described. 31 …”