Inhibition of Plasmodium Hepatic Infection by Antiretroviral Compounds
Recent WHO guidelines on control of human immunodeficiency virus (HIV) call for the widespread use of antiretroviral (AR) therapy (ART) for people living with HIV. Given the considerable overlap between infections by HIV and Plasmodium, the causative agent of malaria, it is important to understand t...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-07-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fcimb.2017.00329/full |
| _version_ | 1818990537621897216 |
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| author | Marta Machado Margarida Sanches-Vaz João P. Cruz António M. Mendes Miguel Prudêncio |
| author_facet | Marta Machado Margarida Sanches-Vaz João P. Cruz António M. Mendes Miguel Prudêncio |
| author_sort | Marta Machado |
| collection | DOAJ |
| description | Recent WHO guidelines on control of human immunodeficiency virus (HIV) call for the widespread use of antiretroviral (AR) therapy (ART) for people living with HIV. Given the considerable overlap between infections by HIV and Plasmodium, the causative agent of malaria, it is important to understand the impact of AR compounds and ART regimens on infections by malaria parasites. We undertook a systematic approach to identify AR drugs and ART drug combinations with inhibitory activity against the obligatory hepatic stage of Plasmodium infection. Our in vitro screen of a wide array of AR drugs identified the non-nucleoside reverse transcriptase inhibitors efavirenz and etravirine (ETV), and the protease inhibitor nelfinavir, as compounds that significantly impair the development of the rodent malaria parasite P. berghei in an hepatoma cell line. Furthermore, we show that WHO-recommended ART drug combinations currently employed in the field strongly inhibit Plasmodium liver infection in mice, an effect that may be significantly enhanced by the inclusion of ETV in the treatment. Our observations are the first report of ETV as an anti-Plasmodial drug, paving the way for further evaluation and potential use of ETV-containing ARTs in regions of geographical overlap between HIV and Plasmodium infections. |
| first_indexed | 2024-12-20T19:55:57Z |
| format | Article |
| id | doaj.art-4015456fe4444109b0ac9af764cd927c |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-20T19:55:57Z |
| publishDate | 2017-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-4015456fe4444109b0ac9af764cd927c2022-12-21T19:28:09ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882017-07-01710.3389/fcimb.2017.00329266732Inhibition of Plasmodium Hepatic Infection by Antiretroviral CompoundsMarta Machado0Margarida Sanches-Vaz1João P. Cruz2António M. Mendes3Miguel Prudêncio4Faculdade de Medicina, Instituto de Medicina Molecular, Universidade de LisboaLisboa, PortugalFaculdade de Medicina, Instituto de Medicina Molecular, Universidade de LisboaLisboa, PortugaliMed.UL-Research Institute for Medicines and Pharmaceutical Sciences, Faculdade de Farmácia da Universidade de LisboaLisboa, PortugalFaculdade de Medicina, Instituto de Medicina Molecular, Universidade de LisboaLisboa, PortugalFaculdade de Medicina, Instituto de Medicina Molecular, Universidade de LisboaLisboa, PortugalRecent WHO guidelines on control of human immunodeficiency virus (HIV) call for the widespread use of antiretroviral (AR) therapy (ART) for people living with HIV. Given the considerable overlap between infections by HIV and Plasmodium, the causative agent of malaria, it is important to understand the impact of AR compounds and ART regimens on infections by malaria parasites. We undertook a systematic approach to identify AR drugs and ART drug combinations with inhibitory activity against the obligatory hepatic stage of Plasmodium infection. Our in vitro screen of a wide array of AR drugs identified the non-nucleoside reverse transcriptase inhibitors efavirenz and etravirine (ETV), and the protease inhibitor nelfinavir, as compounds that significantly impair the development of the rodent malaria parasite P. berghei in an hepatoma cell line. Furthermore, we show that WHO-recommended ART drug combinations currently employed in the field strongly inhibit Plasmodium liver infection in mice, an effect that may be significantly enhanced by the inclusion of ETV in the treatment. Our observations are the first report of ETV as an anti-Plasmodial drug, paving the way for further evaluation and potential use of ETV-containing ARTs in regions of geographical overlap between HIV and Plasmodium infections.http://journal.frontiersin.org/article/10.3389/fcimb.2017.00329/fullPlasmodiumliver stagemalariaHIVAIDSantiretrovirals |
| spellingShingle | Marta Machado Margarida Sanches-Vaz João P. Cruz António M. Mendes Miguel Prudêncio Inhibition of Plasmodium Hepatic Infection by Antiretroviral Compounds Frontiers in Cellular and Infection Microbiology Plasmodium liver stage malaria HIV AIDS antiretrovirals |
| title | Inhibition of Plasmodium Hepatic Infection by Antiretroviral Compounds |
| title_full | Inhibition of Plasmodium Hepatic Infection by Antiretroviral Compounds |
| title_fullStr | Inhibition of Plasmodium Hepatic Infection by Antiretroviral Compounds |
| title_full_unstemmed | Inhibition of Plasmodium Hepatic Infection by Antiretroviral Compounds |
| title_short | Inhibition of Plasmodium Hepatic Infection by Antiretroviral Compounds |
| title_sort | inhibition of plasmodium hepatic infection by antiretroviral compounds |
| topic | Plasmodium liver stage malaria HIV AIDS antiretrovirals |
| url | http://journal.frontiersin.org/article/10.3389/fcimb.2017.00329/full |
| work_keys_str_mv | AT martamachado inhibitionofplasmodiumhepaticinfectionbyantiretroviralcompounds AT margaridasanchesvaz inhibitionofplasmodiumhepaticinfectionbyantiretroviralcompounds AT joaopcruz inhibitionofplasmodiumhepaticinfectionbyantiretroviralcompounds AT antoniommendes inhibitionofplasmodiumhepaticinfectionbyantiretroviralcompounds AT miguelprudencio inhibitionofplasmodiumhepaticinfectionbyantiretroviralcompounds |