Abstract
The present armamentarium of 19 antiretroviral drugs licensed for treatment of HIV-1 infection in the U.S. exemplifies preponderance of scientific evidence, which led to improved understanding of the structural and functional, viral and cellular attributes driving HIV-1 infection. The majority of approved drugs (with exception of enfuvirtide), however, focus on two steps of the viral life cycle: reverse transcription and viral maturation. Therefore, it appears there is ample opportunity for the development of a third drug class that has been extensively researched in recent years known as entry inhibitors. Currently, this class of compounds targets steps involved in virion attachment to CD4 or to an appropriate chemokine receptor on the cell surface as well as subsequent conformational rearrangements induced in the envelope glycoprotein (gp120/gp41; Env). These inhibitors preclude the fusion of the virion envelope with the host cell membrane thereby preventing the release of viral capsid into the cytosol. Antiviral agents interfering with receptor (i.e., CD4) or coreceptor (e.g., CCR5 and/or CXCR4) engagement comprise a special subset of viral entry inhibitors. While drugs targeting viral entry offer certain advantages over other classes of compounds, they also pose specific challenges. This review focuses on compounds blocking viral attachment to CD4, CCR5 or CXCR4, highlights the challenges they present, and attempts to offer possible solutions.
Keywords: antiviral therapy, viral resistance, coreceptor switch, CXCR4, CCR5, CD4, membrane fusion, Viral entry
Current Pharmaceutical Design
Title: Advances in HIV-1 Entry Inhibitors: Strategies to Interfere with Receptor and CoReceptor Engagement
Volume: 12 Issue: 9
Author(s): Ingrid Markovic
Affiliation:
Keywords: antiviral therapy, viral resistance, coreceptor switch, CXCR4, CCR5, CD4, membrane fusion, Viral entry
Abstract: The present armamentarium of 19 antiretroviral drugs licensed for treatment of HIV-1 infection in the U.S. exemplifies preponderance of scientific evidence, which led to improved understanding of the structural and functional, viral and cellular attributes driving HIV-1 infection. The majority of approved drugs (with exception of enfuvirtide), however, focus on two steps of the viral life cycle: reverse transcription and viral maturation. Therefore, it appears there is ample opportunity for the development of a third drug class that has been extensively researched in recent years known as entry inhibitors. Currently, this class of compounds targets steps involved in virion attachment to CD4 or to an appropriate chemokine receptor on the cell surface as well as subsequent conformational rearrangements induced in the envelope glycoprotein (gp120/gp41; Env). These inhibitors preclude the fusion of the virion envelope with the host cell membrane thereby preventing the release of viral capsid into the cytosol. Antiviral agents interfering with receptor (i.e., CD4) or coreceptor (e.g., CCR5 and/or CXCR4) engagement comprise a special subset of viral entry inhibitors. While drugs targeting viral entry offer certain advantages over other classes of compounds, they also pose specific challenges. This review focuses on compounds blocking viral attachment to CD4, CCR5 or CXCR4, highlights the challenges they present, and attempts to offer possible solutions.
Export Options
About this article
Cite this article as:
Markovic Ingrid, Advances in HIV-1 Entry Inhibitors: Strategies to Interfere with Receptor and CoReceptor Engagement, Current Pharmaceutical Design 2006; 12 (9) . https://dx.doi.org/10.2174/138161206776055822
DOI https://dx.doi.org/10.2174/138161206776055822 |
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
-
Controlling the Flow of Energy: Inhibition and Stimulation of the Creatine Transporter
Current Enzyme Inhibition Fetal Protein Restriction, Taurine and Islet Plasticity
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Recent Advances in the Diagnosis and Therapy of Primary Adrenal Insufficiency
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Broadening Our View of Protective Antibody Responses Against HIV
Current HIV Research Uptake and Metabolism of the Short-Chain Fatty Acid Butyrate, a Critical Review of the Literature
Current Drug Metabolism NAP and ADNF-9 Protect Normal and Downs Syndrome Cortical Neurons from Oxidative Damage and Apoptosis
Current Pharmaceutical Design Gene Therapy and Targeted Toxins for Glioma
Current Gene Therapy Susceptibility Genes for the Side Effect of Antipsychotics on Body Weight and Obesity
Current Drug Targets Progress and Outlooks in a Genetic Absence Epilepsy Model (WAG/Rij)
Current Medicinal Chemistry Thyroid Hormones and their Metabolites: Biological Roles and Association with Non-Alcoholic Fatty Liver Disease
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) G Protein-Coupled Receptors: Target-Based In Silico Screening
Current Pharmaceutical Design Diagnostic Approach to Mitochondrial Disorders: the Need for a Reliable Biomarker
Current Molecular Medicine Current Understanding of Polymyxin B Applications in Bacteraemia/ Sepsis Therapy Prevention: Clinical, Pharmaceutical, Structural and Mechanistic Aspects
Anti-Infective Agents in Medicinal Chemistry Pleiotropic Effects of Statins: Stabilization of the Vulnerable Atherosclerotic Plaque?
Current Pharmaceutical Design Monoclonal Antibodies Against Viruses and Bacteria: A Survey of Patents
Recent Patents on Anti-Infective Drug Discovery Current and Emerging Therapies in Neuroendocrine Tumors: Impact of Genetic Targets on Clinical Outcomes
Clinical Cancer Drugs From Surface to Nuclear Receptors: The Endocannabinoid Family Extends its Assets
Current Medicinal Chemistry Ovarian Hyperstimulation Syndrome: The Best Approaches for Preven-tion and Treatment: A Mini-Review
Current Women`s Health Reviews Role of α- and β-adrenergic Mechanisms in the Pathogenesis of Pulmonary Injuries Characterized by Edema, Inflammation and Fibrosis
Cardiovascular & Hematological Disorders-Drug Targets Targeting of Adhesion Molecules as a Therapeutic Strategy in Multiple Myeloma
Current Cancer Drug Targets