AI Article Synopsis
- The study investigates the effects of the HIV protease inhibitor nelfinavir, boosted with ritonavir, on excessive cell death (apoptosis) in mouse models of nonviral diseases.
- Results show that protease inhibitors significantly reduce apoptosis and improve tissue health, function, and recovery in various conditions such as hepatitis, shock, and stroke.
- The study concludes that these inhibitors block apoptosis by protecting mitochondrial integrity and preventing the function of a specific mitochondrial pore complex.
Article Abstract
Inhibitors of HIV protease have been shown to have antiapoptotic effects in vitro, yet whether these effects are seen in vivo remains controversial. In this study, we have evaluated the impact of the HIV protease inhibitor (PI) nelfinavir, boosted with ritonavir, in models of nonviral disease associated with excessive apoptosis. In mice with Fas-induced fatal hepatitis, Staphylococcal enterotoxin B-induced shock, and middle cerebral artery occlusion-induced stroke, we demonstrate that PIs significantly reduce apoptosis and improve histology, function, and/or behavioral recovery in each of these models. Further, we demonstrate that both in vitro and in vivo, PIs block apoptosis through the preservation of mitochondrial integrity and that in vitro PIs act to prevent pore function of the adenine nucleotide translocator (ANT) subunit of the mitochondrial permeability transition pore complex.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1142110 | PMC |
| http://dx.doi.org/10.1172/JCI22954 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
HIV-1 protease inhibitors and mechanisms of HIV-1's resistance.
Glob Health Med
December 2024
Experimental Retrovirology Section, HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Current anti-HIV drugs have significantly improved the prognosis of HIV infected patients so much so that it is now considered a chronic disease, and adherence to medications keeps non-detectable amounts of the virus in the body. However, HIV is still able to generate drug resistance substitutions. Protease inhibitors (PIs) in combination with other classes of anti-HIV drugs constitute an important part of the anti-HIV drug regimen.
View Article and Find Full Text PDFSynthesis, Characterization, and antiviral evaluation of New Chalcone-Based Imidazo[1,2-a]pyridine Derivatives: Insights from in vitro and in silico Anti-HIV studies.
Bioorg Chem
December 2024
Laboratory of Molecular Chemistry, Materials and Environment (LCM2E), Department of Chemistry, Multidisciplinary Faculty of Nador, University Mohamed I, 60700 Nador, Morocco. Electronic address:
Given the ease of synthetic accessibility and the promising biological profile demonstrated by both imidazo[1,2-a]pyridine and Chalcone derivatives, a series of Chalcone-based imidazo[1,2-a]pyridine derivatives were synthesized and characterized using H NMR, C NMR, Mass Spectrometry and FTIR techniques. Density functional theory (DFT) was employed to investigate the structural and electronic properties, providing insights into potential reactive sites. The synthesized compounds were evaluated in vitro for their antiviral properties against human immunodeficiency virus type-1 (HIV-1) and human immunodeficiency virus type-2 (HIV-2) in MT-4 cells.
View Article and Find Full Text PDFAntiviral Agents: Structural Basis of Action and Rational Design.
Subcell Biochem
December 2024
Department of Biomedical Sciences, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain.
During the last forty years, significant progress has been made in the development of novel antiviral drugs, mainly crystallizing in the establishment of potent antiretroviral therapies and the approval of drugs eradicating hepatitis C virus infection. Although major targets of antiviral intervention involve intracellular processes required for the synthesis of viral proteins and nucleic acids, a number of inhibitors blocking virus assembly, budding, maturation, entry, or uncoating act on virions or viral capsids. In this review, we focus on the drug discovery process while presenting the currently used methodologies to identify novel antiviral drugs by means of computer-based approaches.
View Article and Find Full Text PDFTriterpene esters from Uncaria rhynchophylla hooks as potent HIV-1 protease inhibitors and their molecular docking study.
Sci Rep
December 2024
Department of Pharmacognosy, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Korea.
Despite significant advancements with combination anti-retroviral agents, eradicating human immunodeficiency virus (HIV) remains a challenge due to adverse effects, adherence issues, and emerging viral resistance to existing therapies. This underscores the urgent need for safer, more effective drugs to combat resistant strains and advance acquired immunodeficiency syndrome (AIDS) therapeutics. Eight triterpene esters (1-8) were identified from Uncaria rhynchophylla hooks.
View Article and Find Full Text PDFPoorer longitudinal growth among HIV exposed compared to unexposed infants in Kenya.
J Acquir Immune Defic Syndr
December 2024
Departments of Epidemiology and Anthropology, University of Washington, Seattle, WA, USA.
Background: Most infants born to women living with HIV (WLH) are HIV-exposed but uninfected exposed infants have poorer growth than HIV-unexposed uninfected children. Few large studies have compared children who are exposed (CHEU) and unexposed (CHUU) in the era of dolutegravir (DTG)-based antiretroviral treatment (ART).
Setting: Longitudinal study of mother-infant CHEU and CHUU pairs in Nairobi and Western Kenya.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!