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Diketopiperazine/piperidine alkaloid as a potential broad-spectrum coronaviral entry inhibitor identified by supercomputer-based virtual screening from a large natural product-based library.
Biomed Pharmacother
January 2025
Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, Mainz 55128, Germany. Electronic address:
The COVID-19 pandemic has underscored the urgent need for antiviral agents capable of targeting a broad range of coronaviruses, including emerging variants of SARS-CoV-2. While vaccines have been pivotal, the search for drugs that can prevent viral entry into host cells remains crucial, especially against evolving viral forms and other coronaviruses. In this study, we investigated natural products as a source of antiviral agents, focusing on their potential to block the spike protein's receptor-binding domain (RBD).
View Article and Find Full Text PDFEffectiveness of bi-monthly long-acting injectable cabotegravir and rilpivirine as maintenance treatment for HIV-1 in the Netherlands: results from the Dutch ATHENA national observational cohort.
Lancet HIV
January 2025
Stichting HIV Monitoring, Amsterdam, Netherlands; Department of Infectious Diseases, Amsterdam Infection & Immunity Institute, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, Netherlands.
Background: Real-world data showing the long-term effectiveness of long-acting injectable cabotegravir and rilpivirine are scarce. We assessed the effectiveness of cabotegravir and rilpivirine in all individuals who switched to cabotegravir and rilpivirine in the Netherlands.
Methods: We used data from the ATHENA cohort, an ongoing observational nationwide HIV cohort in the Netherlands.
HIV Replication Under High-Level Cabotegravir Is Associated with the Appearance of 3'-PPT Mutations, Circular DNA Transcription and Recombination.
Viruses
November 2024
Laboratory Branch, Division of HIV Prevention, National Center for HIV, Viral Hepatitis, STD and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
The HIV integrase inhibitor, dolutegravir (DTG), in the absence of eliciting integrase (int) resistance, has been reported to select mutations in the virus 3'-polypurine tract (3'-PPT) adjacent to the 3'-LTR U3. An analog of DTG, cabotegravir (CAB), has a high genetic barrier to drug resistance and is used in formulations for treatment and long-acting pre-exposure prophylaxis. We examined whether mutations observed for DTG would emerge in vitro with CAB.
View Article and Find Full Text PDFPredictive Efficacy of Dual Therapies Combining Integrase Strand Transfer Inhibitors with Second-Generation Non-Nucleoside Reverse Transcriptase Inhibitors Following HIV-1 Treatment Failure in Cameroon: Implications for the Use of a Long-Acting Therapeutic Strategy in Low- and Middle-Income Countries.
Viruses
November 2024
Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, Cameroon.
Dual therapies (DT) combining integrase strand transfer inhibitors (INSTIs) with second-generation non-nucleoside reverse transcriptase inhibitors (2nd-Gen-NNRTIs) offer new possibilities for HIV treatment to improve adherence. However, drug resistance associated mutations (RAMs) to prior antiretrovirals may jeopardize the efficacy of DT. We herein describe the predicted efficacy of DT combining INSTIs + 2nd-Gen-NNRTI following treatment failure among Cameroonian patients.
View Article and Find Full Text PDFTargeted isolation of diketopiperazines from a deep-sea derived fungus with anti-neuroinflammatory effects.
Bioorg Chem
January 2025
State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, PR China; Ningbo Institute of Marine Medicine, Peking University, Beijing 100191, PR China. Electronic address:
Prenylated indole diketopiperazines represent a diverse array of alkaloids with complex chemical scaffolds and with a wide range of biological activities. Aiming to discover bioactive metabolites with structural novelty, genomic annotation in association with the MS/MS-based molecular networking demonstrated a deep-sea derived fungus Aspergillus puulaauensis F77 containing a profile of diketopiperazines. Targeted separation of the cultured fungus led to the isolation of 19 undescribed austamide-type diketopiperazines namely versicoines A-S.
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