Drug Reprofiling to Identify Potential HIV-1 Protease Inhibitors
The use of protease inhibitors in human immunodeficiency virus type 1 (HIV-1) treatment is limited by adverse effects, including metabolic complications. To address these challenges, efforts are underway in the pursuit of more potent and less toxic HIV-1 protease inhibitors. Repurposing existing dru...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-08-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/17/6330 |
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| author | Sunday N. Okafor Abigail Meyer Jay Gadsden Fadi Ahmed Lilian Guzmán Hashim Ahmed José A. Fernández Romero Pavimol Angsantikul |
| author_facet | Sunday N. Okafor Abigail Meyer Jay Gadsden Fadi Ahmed Lilian Guzmán Hashim Ahmed José A. Fernández Romero Pavimol Angsantikul |
| author_sort | Sunday N. Okafor |
| collection | DOAJ |
| description | The use of protease inhibitors in human immunodeficiency virus type 1 (HIV-1) treatment is limited by adverse effects, including metabolic complications. To address these challenges, efforts are underway in the pursuit of more potent and less toxic HIV-1 protease inhibitors. Repurposing existing drugs offers a promising avenue to expedite the drug discovery process, saving both time and costs compared to conventional de novo drug development. This study screened FDA-approved and investigational drugs in the DrugBank database for their potential as HIV-1 protease inhibitors. Molecular docking studies and cell-based assays, including anti-HIV-1 in vitro assays and XTT cell viability tests, were conducted to evaluate their efficacy. The study findings revealed that CBR003PS, an antibiotic currently in clinical use, and CBR013PS, an investigational drug for treating endometriosis and uterine fibroids, exhibited significant binding affinity to the HIV-1 protease with high stability. Their EC<sub>50</sub> values, measured at 100% cell viability, were 9.4 nM and 36.6 nM, respectively. Furthermore, cell-based assays demonstrated that these two compounds showed promising results, with therapeutic indexes higher than 32. In summary, based on their favorable therapeutic indexes, CBR003PS and CBR013PS show potential for repurposing as HIV-1 protease inhibitors. |
| first_indexed | 2024-03-10T23:16:55Z |
| format | Article |
| id | doaj.art-f83a337ba5534398bbe2aab7a442938f |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T23:16:55Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-f83a337ba5534398bbe2aab7a442938f2023-11-19T08:34:29ZengMDPI AGMolecules1420-30492023-08-012817633010.3390/molecules28176330Drug Reprofiling to Identify Potential HIV-1 Protease InhibitorsSunday N. Okafor0Abigail Meyer1Jay Gadsden2Fadi Ahmed3Lilian Guzmán4Hashim Ahmed5José A. Fernández Romero6Pavimol Angsantikul7Center for Biomedical Research, Population Council, New York, NY 10065, USACenter for Biomedical Research, Population Council, New York, NY 10065, USACenter for Biomedical Research, Population Council, New York, NY 10065, USADepartment of Science, Borough of Manhattan Community College, The City University of New York, 199 Chambers St., New York, NY 10007, USADepartment of Science, Borough of Manhattan Community College, The City University of New York, 199 Chambers St., New York, NY 10007, USACenter for Biomedical Research, Population Council, New York, NY 10065, USACenter for Biomedical Research, Population Council, New York, NY 10065, USACenter for Biomedical Research, Population Council, New York, NY 10065, USAThe use of protease inhibitors in human immunodeficiency virus type 1 (HIV-1) treatment is limited by adverse effects, including metabolic complications. To address these challenges, efforts are underway in the pursuit of more potent and less toxic HIV-1 protease inhibitors. Repurposing existing drugs offers a promising avenue to expedite the drug discovery process, saving both time and costs compared to conventional de novo drug development. This study screened FDA-approved and investigational drugs in the DrugBank database for their potential as HIV-1 protease inhibitors. Molecular docking studies and cell-based assays, including anti-HIV-1 in vitro assays and XTT cell viability tests, were conducted to evaluate their efficacy. The study findings revealed that CBR003PS, an antibiotic currently in clinical use, and CBR013PS, an investigational drug for treating endometriosis and uterine fibroids, exhibited significant binding affinity to the HIV-1 protease with high stability. Their EC<sub>50</sub> values, measured at 100% cell viability, were 9.4 nM and 36.6 nM, respectively. Furthermore, cell-based assays demonstrated that these two compounds showed promising results, with therapeutic indexes higher than 32. In summary, based on their favorable therapeutic indexes, CBR003PS and CBR013PS show potential for repurposing as HIV-1 protease inhibitors.https://www.mdpi.com/1420-3049/28/17/6330HIV-1 proteasedrug repurposingdrug discoveryHIV-1 protease inhibitors |
| spellingShingle | Sunday N. Okafor Abigail Meyer Jay Gadsden Fadi Ahmed Lilian Guzmán Hashim Ahmed José A. Fernández Romero Pavimol Angsantikul Drug Reprofiling to Identify Potential HIV-1 Protease Inhibitors Molecules HIV-1 protease drug repurposing drug discovery HIV-1 protease inhibitors |
| title | Drug Reprofiling to Identify Potential HIV-1 Protease Inhibitors |
| title_full | Drug Reprofiling to Identify Potential HIV-1 Protease Inhibitors |
| title_fullStr | Drug Reprofiling to Identify Potential HIV-1 Protease Inhibitors |
| title_full_unstemmed | Drug Reprofiling to Identify Potential HIV-1 Protease Inhibitors |
| title_short | Drug Reprofiling to Identify Potential HIV-1 Protease Inhibitors |
| title_sort | drug reprofiling to identify potential hiv 1 protease inhibitors |
| topic | HIV-1 protease drug repurposing drug discovery HIV-1 protease inhibitors |
| url | https://www.mdpi.com/1420-3049/28/17/6330 |
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