| Author | Granato, Marcela Q. | |
| Author | Sousa, Ingrid S. | |
| Author | Rosa, Thabatta L. S. A. | |
| Author | Gonçalves, Diego S. | |
| Author | Seabra, Sergio H. | |
| Author | Alviano, Daniela S. | |
| Author | Pessolani, Maria C. V. | |
| Author | Santos, André L. S. | |
| Author | Kneipp, Lucimar F. | |
| Access date | 2020-05-27T16:14:47Z | |
| Available date | 2020-05-27T16:14:47Z | |
| Document date | 2020 | |
| Citation | GRANATO, Marcela Q. et al. Aspartic peptidase of Phialophora verrucosa as target of HIV peptidase inhibitors: blockage of its enzymatic activity and interference with fungal gorwth and macrophage interaction. Journal of Enzyme Inhibition and Medicinal Chemistry, v. 35, n. 1, p. 629-638, 2020. | pt_BR |
| ISSN | 1475-6366 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/41423 | |
| Language | eng | pt_BR |
| Publisher | Taylor & Francis | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Phialophora verrucosa | pt_BR |
| Subject in Portuguese | HIV | pt_BR |
| Subject in Portuguese | Inibidores de peptidase | pt_BR |
| Subject in Portuguese | Peptidase aspártica | pt_BR |
| Subject in Portuguese | Macrófagos | pt_BR |
| Title | Aspartic peptidase of Phialophora verrucosa as target of HIV peptidase inhibitors: blockage of its enzymatic activity and interference with fungal growth and macrophage interaction | pt_BR |
| Type | Article | |
| DOI | 10.1080/14756366.2020.1724994 | |
| 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. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Taxonomia, Bioquímica e Bioprospecção de Fungos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Taxonomia, Bioquímica e Bioprospecção de Fungos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Laboratório de Estudos Avançados de Microorganismos Emergentes e Resistentes. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro, Instituto de Química. Programa de Pós-Graduação em Bioquímica. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Centro Estadual da Zona Oeste. Laboratório de Tecnologia em Cultura de Células. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Laboratório de Estrutura de Microorganismos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Laboratório de Estudos Avançados de Microorganismos Emergentes e Resistentes. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Química. Programa de Pós-Graduação em Bioquímica. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Taxonomia, Bioquímica e Bioprospecção de Fungos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Subject | Aspartic peptidase | pt_BR |
| Subject | Phialophora verrucosa | pt_BR |
| Subject | HIV | pt_BR |
| Subject | Peptidase inhibitors | pt_BR |
| Subject | Fungal growth | pt_BR |
| Subject | Macrophage | pt_BR |
| e-ISSN | 1475-6374 | |
