AI Article Synopsis
- Researchers discovered DNA helix-based HIV-1 fusion inhibitors that show promise as effective drug candidates.
- Two novel nucleoside analogues were created and integrated into four different DNA-based inhibitor structures, all demonstrating anti-HIV-1 fusion activity.
- The study examined how different hydrophobic groups and linkers influenced helix formation, thermal stability, and variability in reaction targets among inhibitors with similar DNA structures.
Article Abstract
DNA helix-based HIV-1 fusion inhibitors have been discovered as potent drug candidates. Introduction of hydrophobic groups to a nucleobase provides an opportunity to design inhibitors with novel structures and mechanisms of action. In this work, two novel nucleoside analogues (1 and 2) were synthesized and incorporated into four DNA duplex- and quadruplex-based inhibitors. All the molecules showed anti-HIV-1 fusion activity. The effect of the p-benzyloxyphenyl group and the attached linker on the helix formation and thermal stability were fully compared and discussed. Surface plasmon resonance analysis further indicated that inhibitors with the same DNA helix may still have variable reaction targets, mainly attributed to the different hydrophobic modifications.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmcl.2018.04.012 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
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 PDFAnti-HIV-1 HSPC-based gene therapy with safety kill switch to defend against and attack HIV-1 infection.
bioRxiv
November 2024
UCLA AIDS Institute, UCLA, Los Angeles, CA, USA, 90024.
Article Synopsis
- HSPC-based gene therapy shows potential for long-term HIV-1 remission after a single treatment, using a lentiviral vector to deliver three anti-HIV-1 genes.
- Two of the genes focus on preventing infection by targeting the CCR5 co-receptor and inhibiting fusion of the virus, while the third gene is designed to attack infected cells.
- The therapy was successful in humanized mouse models, significantly reducing HIV-1 viral load and allowing for safe removal of modified cells if necessary, demonstrating both effectiveness and safety of the approach.
Design of coiled-coil N-peptides against HIV-1 based on a CADD strategy.
Org Biomol Chem
December 2024
NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, P.R. China.
Human Immunodeficiency Virus (HIV) has continued to endanger human health for decades and has a substantial impact on global health defence. Peptide-based fusion inhibitors, as an integral part of Highly Active Anti-Retroviral Therapy (HAART), are effective in preventing and controlling the AIDS epidemic. Nevertheless, the current market leader, Enfuvirtide, is facing numerous challenges in clinical application.
View Article and Find Full Text PDFEvaluating the Use of Sacran, a Polysaccharide Isolated from , as a Possible Microbicide for Preventing HIV-1 Infection.
Viruses
September 2024
Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan.
Article Synopsis
- Sacran is a special substance that comes from a type of blue-green algae and can help protect against HIV, a virus that causes AIDS.
- Since a new treatment for HIV was created, fewer people are dying from AIDS, but the virus is still spreading through sexual contact.
- The study showed that sacran can stop HIV from spreading and might work even better when used with other HIV medicines.
ADS-J21 is a novel HIV-1 entry inhibitor targeting gp41.
Curr Res Microb Sci
July 2024
Hebei Key Laboratory of Analysis and Control of Zoonotic Pathogenic Microorganism, College of Life Sciences, Hebei Agricultural University, Baoding, 071001, China.
Article Synopsis
- HIV-1 envelope glycoprotein gp41 is crucial for the virus to fuse with host cells, making it a target for anti-HIV drugs.
- A new compound named ADS-J21 has been developed, which shares a similar Y-shaped structure with the previously studied ADS-J1 but has a lower molecular weight and shows effective activity against various HIV-1 strains.
- Research showed that ADS-J21 works by blocking the formation of a critical structure (the six-helix bundle) in gp41, paving the way for it to be optimized as a small-molecule fusion inhibitor.
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!