Abstract
HIV-1 Gag is the master orchestrator of particle assembly. The central role of Gag at multiple stages of the HIV lifecycle has led to efforts to develop drugs that directly target Gag and prevent the formation and release of infectious particles. Until recently, however, only the catalytic site protease inhibitors have been available to inhibit late stages of HIV replication. This review summarizes the current state of development of antivirals that target Gag or disrupt late events in the retrovirus lifecycle such as maturation of the viral capsid. Maturation inhibitors represent an exciting new series of antiviral compounds, including those that specifically target CA-SP1 cleavage and the allosteric integrase inhibitors that inhibit maturation by a completely different mechanism. Numerous small molecules and peptides targeting CA have been studied in attempts to disrupt steps in assembly. Efforts to target CA have recently gained considerable momentum from the development of small molecules that bind CA and alter capsid stability at the post-entry stage of the lifecycle. Efforts to develop antivirals that inhibit incorporation of genomic RNA or to inhibit late budding events remain in preliminary stages of development. Overall, the development of novel antivirals targeting Gag and the late stages in HIV replication appears much closer to success than ever, with the new maturation inhibitors leading the way.
Keywords: Gag, HIV, Antiretroviral, Virus assembly, Capsid, Matrix, Nucleocapsid, Allosteric integrase inhibitors, Bevirimat.
Current Topics in Medicinal Chemistry
Title:HIV-1 Gag as an Antiviral Target: Development of Assembly and Maturation Inhibitors
Volume: 16 Issue: 10
Author(s): Paul Spearman
Affiliation:
Keywords: Gag, HIV, Antiretroviral, Virus assembly, Capsid, Matrix, Nucleocapsid, Allosteric integrase inhibitors, Bevirimat.
Abstract: HIV-1 Gag is the master orchestrator of particle assembly. The central role of Gag at multiple stages of the HIV lifecycle has led to efforts to develop drugs that directly target Gag and prevent the formation and release of infectious particles. Until recently, however, only the catalytic site protease inhibitors have been available to inhibit late stages of HIV replication. This review summarizes the current state of development of antivirals that target Gag or disrupt late events in the retrovirus lifecycle such as maturation of the viral capsid. Maturation inhibitors represent an exciting new series of antiviral compounds, including those that specifically target CA-SP1 cleavage and the allosteric integrase inhibitors that inhibit maturation by a completely different mechanism. Numerous small molecules and peptides targeting CA have been studied in attempts to disrupt steps in assembly. Efforts to target CA have recently gained considerable momentum from the development of small molecules that bind CA and alter capsid stability at the post-entry stage of the lifecycle. Efforts to develop antivirals that inhibit incorporation of genomic RNA or to inhibit late budding events remain in preliminary stages of development. Overall, the development of novel antivirals targeting Gag and the late stages in HIV replication appears much closer to success than ever, with the new maturation inhibitors leading the way.
Export Options
About this article
Cite this article as:
Spearman Paul, HIV-1 Gag as an Antiviral Target: Development of Assembly and Maturation Inhibitors, Current Topics in Medicinal Chemistry 2016; 16 (10) . https://dx.doi.org/10.2174/1568026615666150902102143
DOI https://dx.doi.org/10.2174/1568026615666150902102143 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- 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
-
Chemical Modifications and Biological Activities of Polysaccharides
Current Drug Targets Synthesis and <i>In Silico</i> Studies of C-4 Substituted Coumarin Analogues as Anticancer Agents
Current Computer-Aided Drug Design Multiple Roles of Annexin A2 in Post-Transcriptional Regulation of Gene Expressio
Current Protein & Peptide Science Inhibition of TGF- Signaling for the Treatment of Tumor Metastasis and Fibrotic Diseases
Current Signal Transduction Therapy Bone Marrow Culture Yield for the Diagnosis of Opportunistic Diseases in Patients with AIDS and Disseminated Kaposi Sarcoma
Current HIV Research Medicinal Chemistry Insights into Novel HDAC Inhibitors: An Updated Patent Review (2012-2016)
Recent Patents on Anti-Cancer Drug Discovery A Review of Light Sources and Enhanced Targeting for Photodynamic Therapy
Current Medicinal Chemistry Role of PARP Inhibitors in Cancer Biology and Therapy
Current Medicinal Chemistry Glycoconjugates in Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Indole-3-Carbinol (I3C) and its Major Derivatives: Their Pharmacokinetics and Important Roles in Hepatic Protection
Current Drug Metabolism Synthesis and Characterization of Ibandronate-Loaded Silica Nanoparticles and Collagen Nanocomposites
Current Pharmaceutical Biotechnology Application of Phage Display Technology to Cancer Research
Current Pharmaceutical Biotechnology Carbohydrate Scaffolds for the Production of Bioactive Compounds
Current Organic Synthesis Phycobilins and Phycobiliproteins Used in Food Industry and Medicine
Mini-Reviews in Medicinal Chemistry The Epidermal Growth Factor Receptor as a Therapeutic Target in Glioblastoma Multiforme and other Malignant Neoplasms
Anti-Cancer Agents in Medicinal Chemistry Nucleic Acid Aptamers Against Protein Kinases
Current Medicinal Chemistry A Natural Membrane Vesicle Exosome-based Sinomenine Delivery Platform for Hepatic Carcinoma Therapy
Current Topics in Medicinal Chemistry Selenosemicarbazone Metal Complexes as Potential Metal-based Drugs
Current Medicinal Chemistry Vascular Targeting: A New Antitumor Activity
Drug Design Reviews - Online (Discontinued) Tyrosine Kinase Inhibitors (TKIs) in Lung Cancer Treatment: A Comprehensive Analysis
Current Cancer Drug Targets