Zintevir is an oligonucleotide analogue, which has the phosphorothioate modification at both termini, that forms a K(+)-induced quadruplex structure and shows potent anti-human immunodeficiency virus (HIV)-1 activity. We synthesized the non-modified analogue (D-17mer) of Zintevir and its enantiomer (L-17mer), and compared their anti-HIV-1 activity and molecular mechanism of action. Although L-17mer forms the exact mirror image quadruplex structure of D-17mer, which has a very similar structure with Zintevir, L-17mer showed comparable anti-HIV-1 activity with Zintevir. The results obtained by the time-of-addition experiments and the immunofluorescence binding assay strongly suggest that the primary molecular target of L-17mer is the viral gp120 envelope protein as well as Zintevir, regardless of their reciprocal chirality.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bbrc.2003.11.094 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Structure-based discovery of novel diarylpyrimidines as potent and selective Non-Nucleoside reverse transcriptase inhibitors: From CH(CN)-Biphenyl-Diarylpyrimidines to CNNH-Biphenyl-Diarylpyrimidines.
Eur J Med Chem
January 2025
Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China; Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai, 200433, China; Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs, Shanghai, 200433, China; Institute of Flow Chemistry and Engineering, School of Chemistry and Materials, Jiangxi Normal University, Nanchang, 330022, China. Electronic address:
In order to enhance the anti-HIV-1 potency and selectivity of the previously reported compound 3 (EC = 27 nM, SI = 1361), a series of novel biphenyl-diarylpyrimidine derivatives were developed by employing structure-based drug design strategy. Among these derivatives, compound M44 demonstrated the most potent inhibitory activity against wild-type (WT) HIV-1 as well as five drug-resistant mutants (EC = 5-148 nM), which were 5-173 times more potent than that of 3 (EC = 27-9810 nM). Furthermore, this analogue exhibited approximately 11-fold lower cytotoxicity (CC = 54 μM) than that of etravirine and rilpivirine.
View Article and Find Full Text PDFRole of follicular homing natural killer cells in HIV infection.
Curr Opin HIV AIDS
January 2025
Department of Pathology and Laboratory Medicine, Emory Vaccine Center, Emory National Primate Research Center (ENPRC).
Purpose Of Review: Natural killer (NK) cells are integral components of the innate immune system, serving a vital function in eliminating virally infected cells. This review highlights the significance of CXCR5+ NK cells in the context of chronic HIV/SIV infection and viral control.
Recent Findings: Controlled HIV/SHIV infection results in a substantial increase in the population of CXCR5+ NK cells within the B-cell follicles of secondary lymphoid organs (SLOs).
Two Disaccharide-Bearing Polyethers, K-41B and K-41Bm, Potently Inhibit HIV-1 via Mechanisms Different from That of Their Precursor Polyether, K-41A.
Curr Issues Mol Biol
November 2024
Guangxi Key Laboratory of AIDS Prevention and Treatment, School of Public Health, Guangxi Medical University, Nanning 530021, China.
The screening of novel antiviral agents from marine microorganisms is an important strategy for new drug development. Our previous study found that polyether K-41A and its analog K-41Am, derived from a marine Streptomyces strain, exhibit anti-HIV activity by suppressing the activities of HIV-1 reverse transcriptase (RT) and its integrase (IN). Among the K-41A derivatives, two disaccharide-bearing polyethers-K-41B and K-41Bm-were found to have potent anti-HIV-1 activity in vitro.
View Article and Find Full Text PDFHSP60 controls mitochondrial ATP generation for optimal virus-specific IL-21-producing CD4 and cytotoxic CD8 memory T cell responses.
Commun Biol
December 2024
Institut national de la recherche scientifique (INRS)-Centre Armand-Frappier Santé Biotechnologie, 531 boulevard des Prairies, H7V 1M7, Laval, QC, Canada.
We have shown that virus-specific CD4 and CD8 memory T cells (TM) induce autophagy after T cell receptor (TCR) engagement to provide free glutamine and fatty acids, including in people living with HIV-1 (PLWH). These nutrients fuel mitochondrial ATP generation through glutaminolysis and fatty acid oxidation (FAO) pathways, to fulfill the bioenergetic demands for optimal IL-21 and cytotoxic molecule production in CD4 and CD8 cells, respectively. Here, we expand our knowledge on how the metabolic events that occur in the mitochondria of virus-specific TM down-stream of the autophagy are regulated.
View Article and Find Full Text PDFStructural aspects of HIV-1 integrase inhibitors: SAR studies and synthetic strategies.
Mol Divers
December 2024
Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Moga, Punjab, India.
Acquired immunodeficiency syndrome (AIDS) poses a significant threat to life. Antiretroviral therapy is employed to diminish the replication of the human immunodeficiency virus (HIV), extending life expectancy and improving the quality of patients' lives. These HIV-1 integrase inhibitors form robust covalent interactions with Mg ions, contributing to their tight binding, thereby inhibiting the integration of viral DNA into the CD4 cell DNA.
View Article and Find Full Text PDFWant 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!