Abstract
HIV envelope glycoprotein transmembrane subunit gp41 plays a critical role in the fusion between viral and target cell membranes. Upon gp120 binding to CD4 and a coreceptor (CCR5 or CXCR4), gp41 changes its conformation by forming N-helix trimer between N-heptad repeats (NHRs) and then six-helix bundle between the N-trimer and the Cheptad repeats (CHRs). Peptides derived from the NHR and CHR of gp41 extracellular region have demonstrated potent inhibitory activity on the HIV mediated cell fusion. One of these peptides, T-20, became the first success of a new class of anti-HIV agents, named HIV entry inhibitors. However, a relatively long peptide such as T-20 suffers from several limitations including lack of oral bioavailability and high cost of production. Great efforts have been made to develop alternative peptides and proteins with improved anti-HIV-1 activity, increased bioavailability and reduced cost of production. The most promising approach is the development of small molecule HIV entry inhibitors targeting gp41. Any molecule that blocks the process of NHR homotrimerization and the six-helix bundle formation by targeting the gp41 NHR, NHR trimer and CHR may inhibit HIV-mediated membrane fusion. The progress in development of those anti-HIV agents targeting gp41, from polypeptides to small-molecule compounds, is reviewed.
Keywords: HIV, AIDS, entry inhibitors, gp41, gp120
Current Pharmaceutical Design
Title: HIV Entry Inhibitors Targeting gp41: From Polypeptides to Small-Molecule Compounds
Volume: 13 Issue: 2
Author(s): Shuwen Liu, Shuguang Wu and Shibo Jiang
Affiliation:
Keywords: HIV, AIDS, entry inhibitors, gp41, gp120
Abstract: HIV envelope glycoprotein transmembrane subunit gp41 plays a critical role in the fusion between viral and target cell membranes. Upon gp120 binding to CD4 and a coreceptor (CCR5 or CXCR4), gp41 changes its conformation by forming N-helix trimer between N-heptad repeats (NHRs) and then six-helix bundle between the N-trimer and the Cheptad repeats (CHRs). Peptides derived from the NHR and CHR of gp41 extracellular region have demonstrated potent inhibitory activity on the HIV mediated cell fusion. One of these peptides, T-20, became the first success of a new class of anti-HIV agents, named HIV entry inhibitors. However, a relatively long peptide such as T-20 suffers from several limitations including lack of oral bioavailability and high cost of production. Great efforts have been made to develop alternative peptides and proteins with improved anti-HIV-1 activity, increased bioavailability and reduced cost of production. The most promising approach is the development of small molecule HIV entry inhibitors targeting gp41. Any molecule that blocks the process of NHR homotrimerization and the six-helix bundle formation by targeting the gp41 NHR, NHR trimer and CHR may inhibit HIV-mediated membrane fusion. The progress in development of those anti-HIV agents targeting gp41, from polypeptides to small-molecule compounds, is reviewed.
Export Options
About this article
Cite this article as:
Liu Shuwen, Wu Shuguang and Jiang Shibo, HIV Entry Inhibitors Targeting gp41: From Polypeptides to Small-Molecule Compounds, Current Pharmaceutical Design 2007; 13 (2) . https://dx.doi.org/10.2174/138161207779313722
DOI https://dx.doi.org/10.2174/138161207779313722 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Blood-based biomarkers in large-scale screening for neurodegenerative diseases
Disease biomarkers are necessary tools that can be employ in several clinical context of use (COU), ranging from the (early) diagnosis, prognosis, prediction, to monitor of disease state and/or drug efficacy. Regarding neurodegenerative diseases, in particular Alzheimer’s disease (AD), a battery of well-validated biomarkers are available, such as cerebrospinal fluid ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Diabetes mellitus: advances in diagnosis and treatment driving by precision medicine
Diabetes mellitus (DM) is a chronic degenerative metabolic disease with ever increasing prevalence worldwide which is now an epidemic disease affecting 500 million people worldwide. Insufficient insulin secretion from pancreatic β cells unable to maintain blood glucose homeostasis is the main feature of this disease. Multifactorial and complex nature of ...read more
![](/images/wayfinder.jpg)
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Nab-Paclitaxel in Metastatic Breast Cancer: Defining the Best Patient Profile
Current Cancer Drug Targets Antiproliferative and Antioxidant Potential of Leaf and Leaf Derived Callus Extracts of Aerva lanata (L.) Juss. Ex Schult. Against Human Breast Cancer (MCF-7) Cell Lines
The Natural Products Journal Human Defensins: Synthesis and Structural Properties
Current Pharmaceutical Design Bioluminescent Proteins Prediction with Voting Strategy
Current Bioinformatics Cytotoxic Effects of <i>Garcinia mangostana</i> Pericarp Extract on Cancer Cell Lines
Current Drug Discovery Technologies Nano-based Herbal Medicine: A New Candidate for Prostate Cancer Treatment?
Current Traditional Medicine Poly(lactide-co-glycolide)-based Micro and Nanoparticles for the Controlled Drug Delivery of Vitamins
Current Nanoscience Possibilities of Two-Dimensional Gel Electrophoresis in the Understanding of Human Disease
Current Proteomics Suppression of Inflammatory and Allergic Responses by Pharmacologically Potent Fungus Ganoderma lucidum
Recent Patents on Inflammation & Allergy Drug Discovery A Survey on Machine Learning Based Medical Assistive Systems in Current Oncological Sciences
Current Medical Imaging Interactive Effect of Cigarette Smoking and Gene Variants for Predisposing to Cardiovascular Disease
Current Pharmaceutical Design Bioavailability and Pharmacokinetics of Genistein: Mechanistic Studies on its ADME
Anti-Cancer Agents in Medicinal Chemistry Targeting Ion Channels in Cancer: A Novel Frontier in Antineoplastic Therapy
Current Medicinal Chemistry Bioprocessing of Plant In Vitro Systems for the Mass Production of Pharmaceutically Important Metabolites: Paclitaxel and its Derivatives
Current Medicinal Chemistry Imatinib Reduces the Vasculogenic Potential of Plastic Tumor Cells
Current Angiogenesis (Discontinued) Hypomethylation of Urokinase (uPA) Promoter in Breast and Prostate Cancer: Prognostic and Therapeutic Implications
Current Cancer Drug Targets Vitamin E and Prostate Cancer: Current Evidence and Future Directions
Current Nutrition & Food Science Saponins as Tool for Improved Targeted Tumor Therapies
Current Drug Targets Preclinical and Clinical Efficacy of the Bisphosphonate Ibandronate in Cancer Treatment
Current Clinical Pharmacology Pioglitazone and Cancer: Angel or Demon?
Current Pharmaceutical Design