Quantitative structure-activity relationships (QSAR) for HIV-1 protease inhibitory activity of substituted tetrahydropyrimidinones have been produced using CODESSA PRO methodology and software. The best four-parameter equation (R(2)(cv)=0.847) allowed us to reveal two main structural factors which are strongly correlated with the title activity: molecular hydrophobicity and ability to form hydrogen bonds with the target enzyme.
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http://dx.doi.org/10.1016/s0960-894x(02)00741-2 | DOI Listing |
J Glob Antimicrob Resist
January 2025
Faculty of Medicine, Department of Microbiology, University of Tartu, Tartu, Estonia.
Objectives: We investigated the prevalence of drug resistance mutations (DRMs) in individuals newly diagnosed with HIV-1 in Estonia in 2020 and 2022, and in Ukrainian war refugees living with HIV who arrived in Estonia in 2022.
Methods: HIV-1 genomic RNA was sequenced in protease-reverse transcriptase and integrase regions. DRMs were determined separately by Stanford University CPR Tool and HIVdb Program.
Viruses
December 2024
Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
Treatment options for viral infections are limited and viruses have proven adept at evolving resistance to many existing therapies, highlighting a significant vulnerability in our defenses. In response to this challenge, we explored the modulation of cellular RNA metabolic processes as an alternative paradigm to antiviral development. Previously, the small molecule 5342191 was identified as a potent inhibitor of HIV-1 replication by altering viral RNA accumulation at doses that minimally affect host gene expression.
View Article and Find Full Text PDFJ Biomol Struct Dyn
January 2025
Laboratory of Biology and Health, URAC 34, Faculty of Sciences, Ben M'Sik Hassan II University of Casablanca, Casablanca, Morocco.
The recent spread of SARS-CoV-2 has led to serious concerns about newly emerging infectious coronaviruses. Drug repurposing is a practical method for rapid development of antiviral agents. The viral spike protein of SARS-CoV-2 binds to its major receptor ACE2 to promote membrane fusion.
View Article and Find Full Text PDFJ Antimicrob Chemother
January 2025
CH Tourcoing, Service Universitaire des Maladies Infectieuses, 59200 Tourcoing, France.
Introduction: The specificity of HIV-1 DNA genotypic resistance tests (GRTs) is hampered by the detection of the APOBEC-context drug resistance mutations (AC DRMs), usually harboured by replication-incompetent proviruses. We sought factors associated with defective sequences in the HIV-1 pol region. In addition, AC DRMs and their link with defective sequences were investigated.
View Article and Find Full Text PDFBioorg Med Chem Lett
January 2025
Department of Infectious Diseases, Kumamoto University School of Medicine, Kumamoto 860-8556, Japan; Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo 162-8655, Japan; Experimental Retrovirology Section, HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
We describe here the design, synthesis, and X-ray structural studies of a new class of HIV-1 protease inhibitors containing 8-oxabicyclo[3.2.1]octanol-derived P2 ligands.
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