Abstract
The HIV-1 reverse transcriptase (RT) is one of the most attracting targets for the development of early phase infection inhibitors. Although many RT inhibitors have been approved for the treatment of HIV-1 infection, they all target the polymerase function of this enzyme. So far, no drugs are available for the inhibition of the RT associated ribonuclease H function (RNase H), which plays an essential role in the HIV replication cycle. Moreover it should be reported that many of the known RT inhibitors, targeting the polymerase function, enhance the RNase H activity, indicating that, although spatially distinct, a close relation occurs between the two functions. The aim of this review is to summarise the efforts in the design of new inhibitors either characterized by a novel mechanism of action or capable of blocking both RT associated functions, as well as pointing out the main binding features of the known RT inhibitors.
Keywords: HIV, RT binding pockets and novel inhibitors
Current Pharmaceutical Design
Title:Molecular Aspects of the RT/drug Interactions. Perspective of Dual Inhibitors
Volume: 19 Issue: 10
Author(s): Simona Distinto, Elias Maccioni, Rita Meleddu, Angela Corona, Stefano Alcaro and Enzo Tramontano
Affiliation:
Keywords: HIV, RT binding pockets and novel inhibitors
Abstract: The HIV-1 reverse transcriptase (RT) is one of the most attracting targets for the development of early phase infection inhibitors. Although many RT inhibitors have been approved for the treatment of HIV-1 infection, they all target the polymerase function of this enzyme. So far, no drugs are available for the inhibition of the RT associated ribonuclease H function (RNase H), which plays an essential role in the HIV replication cycle. Moreover it should be reported that many of the known RT inhibitors, targeting the polymerase function, enhance the RNase H activity, indicating that, although spatially distinct, a close relation occurs between the two functions. The aim of this review is to summarise the efforts in the design of new inhibitors either characterized by a novel mechanism of action or capable of blocking both RT associated functions, as well as pointing out the main binding features of the known RT inhibitors.
Export Options
About this article
Cite this article as:
Distinto Simona, Maccioni Elias, Meleddu Rita, Corona Angela, Alcaro Stefano and Tramontano Enzo, Molecular Aspects of the RT/drug Interactions. Perspective of Dual Inhibitors, Current Pharmaceutical Design 2013; 19 (10) . https://dx.doi.org/10.2174/1381612811319100009
DOI https://dx.doi.org/10.2174/1381612811319100009 |
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
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
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Axonopathy Likely Initiates Neuropathological Processes Via a Mechanism of Axonal Leakage in Alzheimer's Mouse Models
Current Molecular Medicine Hybrid Stress Testing by Adenosine Infusion and Exercise Myocardial Perfusion Imaging: A Critical Appraisal
Current Cardiology Reviews Systematic Review of Local Studies Regarding Efficiency of Add-On Medications on Negative Symptoms of Schizophrenia: A Meta-Analysis
Current Psychopharmacology Liposomes: An Emerging Approach for the Treatment of Cancer
Current Pharmaceutical Design Secondary Brain Injuries in Thalamus and Hippocampus after Focal Ischemia Caused by Mild, Transient Extradural Compression of the Somatosensori Cortex in the Rat
Current Neurovascular Research CIAPIN1 siRNA Inhibits Proliferation, Migration and Promotes Apoptosis of VSMCs by Regulating Bcl-2 and Bax
Current Neurovascular Research The Effects of Aging on Haptic Working Memory During Length Discrimination
Neuroscience and Biomedical Engineering (Discontinued) The Role of Osteopontin in Experimental Autoimmune Encephalomyelitis (EAE) and Multiple Sclerosis (MS)
Inflammation & Allergy - Drug Targets (Discontinued) Releasing the Genie in the Bottle: Molecular Signaling with Hydrogen Sulfide
Current Neurovascular Research Pharmacological Regulation of Parathyroid Hormone Secretion
Current Pharmaceutical Design Editorial (Thematic Issue: Allosteric Modulators of G Protein-Coupled Receptors)
Current Topics in Medicinal Chemistry In Silico Studies Most Employed in the Discovery of New Antimicrobial Agents
Current Medicinal Chemistry Meet Our Editorial Board Member
Current Alzheimer Research The Ryanodine Receptor: A Pivotal Ca2+ Regulatory Protein and Potential Therapeutic Drug Target
Current Drug Targets Emerging Signalling and Protein Interactions Mediated Via Metabotropic Glutamate Receptors
Current Drug Targets - CNS & Neurological Disorders Myogenic Potential of Mesenchymal Stem Cells - the Case of Adhesive Fraction of Human Umbilical Cord Blood Cells
Current Stem Cell Research & Therapy Neuropsychological Findings in Obsessive-Compulsive Disorder and its Potential Implications for Treatment
Current Psychiatry Reviews Role of Neuroimaging Modality in the Assessment of Oxidative Stress in Brain: A Comprehensive Review
CNS & Neurological Disorders - Drug Targets Inorganic Materials for Applications in Hybrid Solar Cells
Current Inorganic Chemistry (Discontinued) High Throughput Screening and Structure-Activity Relationship Study of Potential α2A-Adrenoceptor Agonists by LANCETM cAMP Assay
Combinatorial Chemistry & High Throughput Screening