The design and synthesis of a novel series of non-nucleoside HIV reverse transcriptase inhibitors (NNRTIs) based on a pyrazole template is described. These compounds are active against wild type reverse transcriptase (RT) and retain activity against clinically important mutants.
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http://dx.doi.org/10.1016/j.bmcl.2009.08.039 | DOI Listing |
J Acquir Immune Defic Syndr
January 2025
MSD France, Puteaux, France.
Background: Neuropsychiatric adverse events (NPAEs) are associated with several antiretrovirals. Doravirine (DOR), a non-nucleoside reverse transcriptase inhibitor indicated for HIV-1 treatment, does not interact significantly with known neurotransmitter receptors in vitro. First-line therapy with DOR-based regimens resulted in significantly fewer NPAEs than efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) and similar rates to those of ritonavir-boosted darunavir (DRV/r) with 2 nucleos(t)ide reverse transcriptase inhibitors (NRTIs) through Week 96 of the phase 3 DRIVE-AHEAD and DRIVE-FORWARD studies, respectively.
View Article and Find Full Text PDFCommun Chem
January 2025
Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Flemingovo nam. 2, CZ-16000 Prague 6, Prague, Czech Republic.
Protein-RNA interactions play important biological roles and hence reactive RNA probes for cross-linking with proteins are important tools in their identification and study. To this end, we designed and synthesized 5'-O-triphosphates bearing a reactive squaramate group attached to position 5 of cytidine or position 7 of 7-deazaadenosine and used them as substrates for polymerase synthesis of modified RNA. In vitro transcription with T7 RNA polymerase or primer extension using TGK polymerase was used for synthesis of squaramate-modified RNA probes which underwent covalent bioconjugations with amine-linked fluorophore and lysine-containing peptides and proteins including several viral RNA polymerases or HIV reverse transcriptase.
View Article and Find Full Text PDFCell Rep
December 2024
Westlake Genetech, Ltd., No. 1 Yunmeng Road, Cloud Town, Hangzhou 310024, China; School of Life Sciences, Westlake University, 600 Dunyu Road, Hangzhou 310030, China. Electronic address:
Efficient prime editor (PE) delivery in vivo is critical for realizing its full potential in disease modeling and therapeutic correction. Although PE has been divided into two halves and delivered using dual adeno-associated viruses (AAVs), the editing efficiency at different gene loci varies among split sites. Furthermore, efficient split sites within Cas9 nickase (Cas9n) are limited.
View Article and Find Full Text PDFJ Acquir Immune Defic Syndr
January 2025
Makerere University - Johns Hopkins University Research Collaboration, Kampala, Uganda.
Introduction: We assessed the risk of adverse pregnancy and birth outcomes and birth defects among women living with HIV (WLHIV) on antiretroviral therapy (ART) and HIV-negative women.
Methods: We analyzed data on live births, stillbirths, and spontaneous abortions during 2015-2021 from a hospital-based birth defects surveillance system in Kampala, Uganda. ART regimens were recorded from hospital records and maternal self-reports.
Appl Environ Microbiol
December 2024
Centre National de Référence des virus des gastro-entérites, Centre Hospitalier Universitaire Dijon Bourgogne, Dijon, France.
Human Aichi virus 1 (AiV-1) is a water- and food-borne infection-associated picornavirus that causes gastroenteritis in humans. Recent studies on environmental waters showed a high frequency and abundance of AiV-1, suggesting that it might be an appropriate indicator of fecal contamination. We screened 450 surface and drinking water samples from a Tunisian drinking water treatment plant (DWTP) and the Sidi Salem dam for AiV-1 by real time reverse transcriptase PCR (RT-qPCR).
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