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
-
Imaging Studies in Hypercalcemia
Current Medicinal Chemistry The Role of the Endocannabinoid System in Eating Disorders: Neurochemical and Behavioural Preclinical Evidence
Current Pharmaceutical Design Is there a Role for Cortisol in the Accumulation of Lipids in the Intima a Crucial Step of Atherogenesis?
Current Vascular Pharmacology CB1 Cannabinoid Antagonists: Structure-Activity Relationships and Potential Therapeutic Applications
Current Topics in Medicinal Chemistry Vitiligo: Pathogenetic Hypotheses and Targets for Current Therapies
Current Drug Metabolism 5-HT2C Receptor Agonists as Potential Drugs for the Treatment of Obesity
Current Topics in Medicinal Chemistry The Recent Progresses on The Improved Therapy of Melanoma by Novel Drug Delivery Systems
Current Drug Targets Mouse Models of Autoimmune Diseases - Autoimmune Myocarditis
Current Pharmaceutical Design Development of Novel, Highly Cytotoxic Fusion Constructs Containing Granzyme B: Unique Mechanisms and Functions
Current Pharmaceutical Design Protective Role of Diabetes Mellitus on Abdominal Aortic Aneurysm Pathogenesis: Myth or Reality?
Current Vascular Pharmacology The Development of Cannabinoid CBII Receptor Agonists for the Treatment of Central Neuropathies
Central Nervous System Agents in Medicinal Chemistry Lipids and Lysosomes
Current Drug Metabolism Current and Future Applications for Stem Cell Therapies in Spine Surgery
Current Stem Cell Research & Therapy Extracellular Matrix on the Phenotypic Switching of Vascular Smooth Muscle Cells
Current Angiogenesis (Discontinued) The Prospect for Type 2 Diabetes Mellitus Combined with Exercise and Synbiotics: A Perspective
Current Diabetes Reviews Craniofacial Anomalies: From Development to Molecular Pathogenesis
Current Molecular Medicine Antihypertensive Treatment with Beta-Blockers in the Metabolic Syndrome: A Review
Current Diabetes Reviews Serotonin Transporter Gene Variants and Behavior: A Comprehensive Review
Current Drug Targets Current and Emerging Therapeutic Approaches in HCV-Related Mixed Cryoglobulinemia
Current Medicinal Chemistry Pharmacological Inhibition of Interleukin-8 (CXCL8) as a New Approach for the Prevention and Treatment of Several Human Diseases
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents