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ASPARTIC PEPTIDASE OF PHIALOPHORA VERRUCOSA AS TARGET OF HIV PEPTIDASE INHIBITORS: BLOCKAGE OF ITS ENZYMATIC ACTIVITY AND INTERFERENCE WITH FUNGAL GROWTH AND MACROPHAGE INTERACTION
HIV
Inibidores de peptidase
Peptidase aspártica
Macrófagos
Author
Affilliation
Abstract
Phialophora verrucosa causes several fungal human diseases, mainly chromoblastomycosis, which is
extremely difficult to treat. Several studies have shown that human immunodeficiency virus peptidase
inhibitors (HIV-PIs) are attractive candidates for antifungal therapies. This work focused on studying the
action of HIV-PIs on peptidase activity secreted by P. verrucosa and their effects on fungal proliferation
and macrophage interaction. We detected a peptidase activity from P. verrucosa able to cleave albumin,
sensitive to pepstatin A and HIV-PIs, especially lopinavir, ritonavir and amprenavir, showing for the first
time that this fungus secretes aspartic-type peptidase. Furthermore, lopinavir, ritonavir and nelfinavir
reduced the fungal growth, causing remarkable ultrastructural alterations. Lopinavir and ritonavir also
affected the conidia-macrophage adhesion and macrophage killing. Interestingly, P. verrucosa had its
growth inhibited by ritonavir combined with either itraconazole or ketoconazole. Collectively, our results
support the antifungal action of HIV-PIs and their relevance as a possible alternative therapy for fungal
infections.
ARTICLE HISTORY
Received 18 December 2019
Revised 27 January 2020
Accepted 28 January 2020
KEYWORDS
Chromoblastomycosis; HIV
peptidase inhibitors;
aspartic peptidase;
antifungal activity; cellular
interactions.
Keywords in Portuguese
Phialophora verrucosaHIV
Inibidores de peptidase
Peptidase aspártica
Macrófagos
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