Drug Reprofiling to Identify Potential HIV-1 Protease Inhibitors

被引:1
|
作者
Okafor, Sunday N. [1 ,2 ]
Meyer, Abigail [1 ,3 ]
Gadsden, Jay [1 ]
Ahmed, Fadi [3 ]
Guzman, Lilian [3 ]
Ahmed, Hashim [1 ]
Romero, Jose A. Fernandez [1 ,3 ]
Angsantikul, Pavimol [1 ]
机构
[1] Ctr Biomed Res, Populat Council, New York, NY 10065 USA
[2] Univ Nigeria, Dept Pharmaceut & Med Chem, Nsukka 41001, Nigeria
[3] CUNY, Borough Manhattan Community Coll, Dept Sci, 199 Chambers St, New York, NY 10007 USA
来源
MOLECULES | 2023年 / 28卷 / 17期
关键词
HIV-1; protease; drug repurposing; drug discovery; HIV-1 protease inhibitors; INSULIN-RESISTANCE; IN-VITRO; INDINAVIR; OXIDATION; THERAPY;
D O I
10.3390/molecules28176330
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 EC50 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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页数:14
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