Abstract
Human immunodeficiency virus (HIV) remains a global health problem. While combined antiretroviral therapy has been successful in controlling the virus in patients, HIV can develop resistance to drugs used for treatment, rendering available drugs less effective and limiting treatment options. Initiatives to find novel drugs for HIV treatment are ongoing, although traditional drug design approaches often focus on known binding sites for inhibition of established drug targets like reverse transcriptase and integrase. These approaches tend towards generating more inhibitors in the same drug classes already used in the clinic. Lack of diversity in antiretroviral drug classes can result in limited treatment options, as cross-resistance can emerge to a whole drug class in patients treated with only one drug from that class. A fresh approach in the search for new HIV-1 drugs is fragment-based drug discovery (FBDD), a validated strategy for drug discovery based on using smaller libraries of low molecular weight molecules (<300 Da) screened using primarily biophysical assays. FBDD is aimed at not only finding novel drug scaffolds, but also probing the target protein to find new, often allosteric, inhibitory binding sites. Several fragment-based strategies have been successful in identifying novel inhibitory sites or scaffolds for two proven drug targets for HIV-1, reverse transcriptase and integrase. While any FBDD-generated HIV-1 drugs have yet to enter the clinic, recent FBDD initiatives against these two well-characterised HIV-1 targets have reinvigorated antiretroviral drug discovery and the search for novel classes of HIV-1 drugs.
Keywords: Antiretrovirals, HIV-1, Fragment-based drug discovery, Reverse transcriptase, Integrase, Fragment screening.
Current Topics in Medicinal Chemistry
Title:Fragment Based Strategies for Discovery of Novel HIV-1 Reverse Transcriptase and Integrase Inhibitors
Volume: 16 Issue: 10
Author(s): Catherine F. Latham, Jennifer La, Ricky N. Tinetti, David K. Chalmers and Gilda Tachedjian
Affiliation:
Keywords: Antiretrovirals, HIV-1, Fragment-based drug discovery, Reverse transcriptase, Integrase, Fragment screening.
Abstract: Human immunodeficiency virus (HIV) remains a global health problem. While combined antiretroviral therapy has been successful in controlling the virus in patients, HIV can develop resistance to drugs used for treatment, rendering available drugs less effective and limiting treatment options. Initiatives to find novel drugs for HIV treatment are ongoing, although traditional drug design approaches often focus on known binding sites for inhibition of established drug targets like reverse transcriptase and integrase. These approaches tend towards generating more inhibitors in the same drug classes already used in the clinic. Lack of diversity in antiretroviral drug classes can result in limited treatment options, as cross-resistance can emerge to a whole drug class in patients treated with only one drug from that class. A fresh approach in the search for new HIV-1 drugs is fragment-based drug discovery (FBDD), a validated strategy for drug discovery based on using smaller libraries of low molecular weight molecules (<300 Da) screened using primarily biophysical assays. FBDD is aimed at not only finding novel drug scaffolds, but also probing the target protein to find new, often allosteric, inhibitory binding sites. Several fragment-based strategies have been successful in identifying novel inhibitory sites or scaffolds for two proven drug targets for HIV-1, reverse transcriptase and integrase. While any FBDD-generated HIV-1 drugs have yet to enter the clinic, recent FBDD initiatives against these two well-characterised HIV-1 targets have reinvigorated antiretroviral drug discovery and the search for novel classes of HIV-1 drugs.
Export Options
About this article
Cite this article as:
Latham F. Catherine, La Jennifer, Tinetti N. Ricky, Chalmers K. David and Tachedjian Gilda, Fragment Based Strategies for Discovery of Novel HIV-1 Reverse Transcriptase and Integrase Inhibitors, Current Topics in Medicinal Chemistry 2016; 16 (10) . https://dx.doi.org/10.2174/1568026615666150901114329
DOI https://dx.doi.org/10.2174/1568026615666150901114329 |
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
-
Patents and the Development on Polymer based Nanomaterial (PAMAM Dendrimer) for Biomedical Applications
Recent Patents on Biomedical Engineering (Discontinued) The Quest for Surrogate Markers of Angiogenesis: A Paradigm for Translational Research in Tumor Angiogenesis and Anti- Angiogenesis Trials
Current Molecular Medicine Isolation and Phenotypic Characterisation of Stem Cells from Late Stage Osteoarthritic Mesenchymal Tissues
Current Stem Cell Research & Therapy Retroviral Gene Therapy: Safety Issues and Possible Solutions
Current Gene Therapy Unmasking Sex-Based Disparity in Neuronal Metabolism
Current Pharmaceutical Design Alphaviruses and their Derived Vectors as Anti-Tumor Agents
Current Cancer Drug Targets Epigenetic Targets and their Inhibitors in Cancer Therapy
Current Topics in Medicinal Chemistry Natural Products to Improve Quality of Life Targeting for Colon Drug Delivery
Current Drug Delivery Nanomedicine to Overcome Cancer Multidrug Resistance
Current Drug Metabolism Drug-Loaded Nanocarriers in Tumor Targeted Drug Delivery
Current Biotechnology Lipoxygenase (LOX) Pathway: A Promising Target to Combat Cancer
Current Pharmaceutical Design Synthesis and Anticancer Studies of Novel N-benzyl Pyridazino ne Derivatives
Letters in Drug Design & Discovery Guaraná a Caffeine-Rich Food Increases Oxaliplatin Sensitivity of Colorectal HT-29 Cells by Apoptosis Pathway Modulation
Anti-Cancer Agents in Medicinal Chemistry Fragment-Based Drug Discovery and Molecular Docking in Drug Design
Current Pharmaceutical Biotechnology Surgical Options for Management of Malignant Pleural Mesothelioma in the Current Era
Current Respiratory Medicine Reviews Immunoglobulin VH Domains and Beyond Design and Selection of Single-Domain Binding and Targeting Reagents
Current Pharmaceutical Biotechnology Expression of Heme Oxygenase-1 in Response to Proteasomal Inhibition
Protein & Peptide Letters Effects of Estrogens on Atherogenesis
Current Vascular Pharmacology Insulin-Like Growth Factor 1 Receptor Targeted Therapeutics: Novel Compounds and Novel Treatment Strategies for Cancer Medicine
Recent Patents on Anti-Cancer Drug Discovery OX40:OX40L Axis: Emerging Targets for Immunotherapy of Human Disease
Current Immunology Reviews (Discontinued)