Two alpha-helical heptad repeats, N-HR and C-HR, located in the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp41, play an important role in membrane fusion by forming a 6-helix bundle. C34, a peptide mimicking C-HR, inhibits the formation of the 6-helix bundle; thus, it has potential as a novel antiretroviral compound. In order to improve the inhibitory effect of C34 on HIV-1 replication, we designed new C34-derived peptides based on computational analysis of the stable conformation of the 6-helix bundle. Newly designed peptides showed a stronger inhibitory effect on the replication of recombinant viruses containing CRF01_AE, subtype B or subtype C Env than C34 or a fusion inhibitor, T-20. In addition, these peptides inhibited the replication of a T-20-resistant virus. We propose that these peptides could be applied to develop novel antiretroviral compounds to inhibit the replication of various subtypes of HIV-1 as well as of T-20-resistant variants.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.virol.2010.06.012 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
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 PDFNon-averaged single-molecule tertiary structures reveal RNA self-folding through individual-particle cryo-electron tomography.
Nat Commun
October 2024
The Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA.
Large-scale and continuous conformational changes in the RNA self-folding process present significant challenges for structural studies, often requiring trade-offs between resolution and observational scope. Here, we utilize individual-particle cryo-electron tomography (IPET) to examine the post-transcriptional self-folding process of designed RNA origami 6-helix bundle with a clasp helix (6HBC). By avoiding selection, classification, averaging, or chemical fixation and optimizing cryo-ET data acquisition parameters, we reconstruct 120 three-dimensional (3D) density maps from 120 individual particles at an electron dose of no more than 168 eÅ, achieving averaged resolutions ranging from 23 to 35 Å, as estimated by Fourier shell correlation (FSC) at 0.
View Article and Find Full Text PDFA Chemo-Mechanically Coupled DNA Origami Clamp Capable of Generating Robust Compression Forces.
Small
October 2024
School of Artificial Intelligence and Automation, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China.
DNA nanostructures have been utilized to study biological mechanical processes and construct artificial nanosystems. Many application scenarios necessitate nanodevices able to robustly generate large single molecular forces. However, most existing dynamic DNA nanostructures are triggered by probabilistic hybridization reactions between spatially separated DNA strands, which only non-deterministically generate relatively small compression forces (≈0.
View Article and Find Full Text PDFMolecular dynamics simulations show how antibodies may rescue HIV-1 mutants incapable of infecting host cells.
J Biomol Struct Dyn
December 2023
Centre for Condensed Matter Theory, Department of Physics, Indian Institute of Science, Bengaluru, India.
High mutation and replication rates of HIV-1 result in the continuous generation of variants, allowing it to adapt to changing host environments. Mutations often have deleterious effects, but variants carrying them are rapidly purged. Surprisingly, a particular variant incapable of entering host cells was found to be rescued by host antibodies targeting HIV-1.
View Article and Find Full Text PDFAssembly and optically triggered disassembly of lipid-DNA origami fibers.
Chem Commun (Camb)
December 2023
Biohybrid Materials, Department of Bioproducts and Biosystems, Aalto University, 00076 Aalto, Finland.
The co-assembly of lipids and other compounds has recently gained increasing interest. Here, we report the formation of stimuli-responsive lipid-DNA origami fibers through the electrostatic co-assembly of cationic lipids and 6-helix bundle (6HB) DNA origami. The photosensitive lipid degrades when exposed to UV-A light, which allows a photoinduced, controlled release of the 6HBs from the fibers.
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!