Abstract
Acquired immunodeficiency syndrome (AIDS) remains, after 25 years of its discovery, as one of the major threats to human life. Reverse Transcriptase is an essential enzyme for virus replication, and therefore constitutes a major target in HIV-1 therapy. Among the different types of drugs targeting RT, the nonnucleoside reverse transcriptase inhibitors (NNRTIs) act by binding in an induced- fit allosteric pocket. In this review, we explore the several NNRTIs structures and binding interactions, as well as their mechanisms of action. The conformational changes that they cause in RT and their effects on the topology of the active site are discussed. The emergence of mutant, resistant viruses is analysed, focussing on the mutations responsible for the loss of antiviral efficacy of NNRTIs. Explanations for the role of those mutations are presented. Emergent drugs in the pipeline, together with the underlying strategies for drug development, are also analysed.
Current Medicinal Chemistry
Title: The Current Status of the NNRTI Family of Antiretrovirals Used Against HIV Infection
Volume: 15 Issue: 11
Author(s): Silvia Martins, Maria Joao Ramos and Pedro Alexandrino Fernandes
Affiliation:
Abstract: Acquired immunodeficiency syndrome (AIDS) remains, after 25 years of its discovery, as one of the major threats to human life. Reverse Transcriptase is an essential enzyme for virus replication, and therefore constitutes a major target in HIV-1 therapy. Among the different types of drugs targeting RT, the nonnucleoside reverse transcriptase inhibitors (NNRTIs) act by binding in an induced- fit allosteric pocket. In this review, we explore the several NNRTIs structures and binding interactions, as well as their mechanisms of action. The conformational changes that they cause in RT and their effects on the topology of the active site are discussed. The emergence of mutant, resistant viruses is analysed, focussing on the mutations responsible for the loss of antiviral efficacy of NNRTIs. Explanations for the role of those mutations are presented. Emergent drugs in the pipeline, together with the underlying strategies for drug development, are also analysed.
Export Options
About this article
Cite this article as:
Martins Silvia, Ramos Joao Maria and Fernandes Alexandrino Pedro, The Current Status of the NNRTI Family of Antiretrovirals Used Against HIV Infection, Current Medicinal Chemistry 2008; 15 (11) . https://dx.doi.org/10.2174/092986708784221467
DOI https://dx.doi.org/10.2174/092986708784221467 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
The Effects of Insulin and Insulin-Like Growth Factors on Tumor Vascularization: New Insights of Insulin-Like Growth Factor Family in Cancer
Current Medicinal Chemistry Peroxynitrite-Driven Mechanisms in Diabetes and Insulin Resistance – the Latest Advances
Current Medicinal Chemistry Anatomical Approach to Clinical Problems of Popliteal Fossa
Current Rheumatology Reviews Immunotherapeutic Options for Pediatric Malignancies
Current Immunology Reviews (Discontinued) Clinical Management of the Cardiovascular Failure in Sepsis
Current Vascular Pharmacology Neuroimaging of the Serotonin Transporter: Possibilities and Pitfalls
Current Psychiatry Reviews Personalized Medicine and Molecular Diagnostics for Obesity: Metabolic Systems Reconstruction and Gut Microbiome Biomarkers
Current Pharmacogenomics and Personalized Medicine Chondromodulin-I and Tenomodulin: The Negative Control of Angiogenesis in Connective Tissue
Current Pharmaceutical Design Age-Related Inflammation: the Contribution of Different Organs, Tissues and Systems. How to Face it for Therapeutic Approaches
Current Pharmaceutical Design From Proteins to Nucleic Acid-Based Drugs: The Role of Biotech in Anti-VEGF Therapy
Anti-Cancer Agents in Medicinal Chemistry Drugs and Rhabdomyolysis: From Liver to Kidney
Current Vascular Pharmacology Targeting Microtubules to Inhibit Angiogenesis and Disrupt Tumour Vasculature:Implications for Cancer Treatment
Current Cancer Drug Targets Assessment of a Novel Vitamin D<sub>3</sub> Formulation with Nanostructured Lipid Carriers for Transdermal Delivery
Current Drug Delivery Cancer Stem Cells: A New Paradigm for Understanding Tumor Growth and Progression and Drug Resistance
Current Medicinal Chemistry Preface
Current Molecular Medicine The Therapeutic Potential of the Wnt Signaling Pathway in Bone Disorders
Current Molecular Pharmacology Microbial Antigenic Pressure and Evolution of the Immune Response: Toward a Better Understanding of the Human Immune System in Health and Disease and Therapeutic Interventions
Endocrine, Metabolic & Immune Disorders - Drug Targets Designing Novel Therapies Against Sarcomas in the Era of Personalized Medicine and Economic Crisis
Current Pharmaceutical Design Mitochondrial Physiology and Toxicity (Mitotoxicity); Importance for the Immune System, Programmed Cell Death and Cancer
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents The Microbiota and Gut-Brain Axis: Contributions to the Immunopathogenesis of Schizophrenia
Current Pharmaceutical Design