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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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Autores principales: Okafor, Sunday N., Meyer, Abigail, Gadsden, Jay, Ahmed, Fadi, Guzmán, Lilian, Ahmed, Hashim, Romero, José A. Fernández, Angsantikul, Pavimol
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10488881/
https://www.ncbi.nlm.nih.gov/pubmed/37687159
http://dx.doi.org/10.3390/molecules28176330
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author Okafor, Sunday N.
Meyer, Abigail
Gadsden, Jay
Ahmed, Fadi
Guzmán, Lilian
Ahmed, Hashim
Romero, José A. Fernández
Angsantikul, Pavimol
author_facet Okafor, Sunday N.
Meyer, Abigail
Gadsden, Jay
Ahmed, Fadi
Guzmán, Lilian
Ahmed, Hashim
Romero, José A. Fernández
Angsantikul, Pavimol
author_sort Okafor, Sunday N.
collection PubMed
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(50) 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.
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spelling pubmed-104888812023-09-09 Drug Reprofiling to Identify Potential HIV-1 Protease Inhibitors Okafor, Sunday N. Meyer, Abigail Gadsden, Jay Ahmed, Fadi Guzmán, Lilian Ahmed, Hashim Romero, José A. Fernández Angsantikul, Pavimol Molecules Article 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(50) 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. MDPI 2023-08-30 /pmc/articles/PMC10488881/ /pubmed/37687159 http://dx.doi.org/10.3390/molecules28176330 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Okafor, Sunday N.
Meyer, Abigail
Gadsden, Jay
Ahmed, Fadi
Guzmán, Lilian
Ahmed, Hashim
Romero, José A. Fernández
Angsantikul, Pavimol
Drug Reprofiling to Identify Potential 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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10488881/
https://www.ncbi.nlm.nih.gov/pubmed/37687159
http://dx.doi.org/10.3390/molecules28176330
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