Abstract
The annual flu season causes thousands of deaths and millions of hospitalizations, which pose a great burden to global health and economy. Moreover, a flu pandemic arising from reassortment viruses, such as H5N1 and H1N1, raises even greater concern due to the lack of effective vaccines at the initial stage of flu outbreak. The influenza virus is the causative agent of flu infection. Currently there are four drugs in use to combat influenza infection. Amantadine and rimantadine are M2 proton channel blockers that inhibit virus uncoating; oseltamivir and zanamivir are neuraminidase (NA) inhibitors that inhibit virus release. However, recent years have witnessed a drastic increase in instances of drug resistance, and flu strains that are resistant to both classes of drugs have been reported. Thus, there is a pressing need to develop the next generation of anti-influenza drugs. Among a handful of anti-influenza drug targets, the viral fusion protein hemagglutinin (HA) is one of the most advanced. This review discusses the biological roles of HA during viral replication and highlights peptide- and small molecule–based HA inhibitors, including recent computationally designed HA binders. The text is organized into four sections based on the maturation stages of HA: inhibitors targeting the glycosylation of HA, the proteolytic activation of HA, the attachment of HA to host cell receptors, and peptide- and small molecule–based inhibitors targeting HA-mediated membrane fusion. Of particular interest are advances in the areas of developing dual inhibitors targeting both HA and NA and broad-spectrum HA inhibitors targeting both groups of HAs.
Keywords: Adamantane, fusion inhibitors, hemagglutinin, influenza, membrane fusion.
Current Medicinal Chemistry
Title:Inhibitors Targeting the Influenza Virus Hemagglutinin
Volume: 22 Issue: 11
Author(s): F. Li, C. Ma and J. Wang
Affiliation:
Keywords: Adamantane, fusion inhibitors, hemagglutinin, influenza, membrane fusion.
Abstract: The annual flu season causes thousands of deaths and millions of hospitalizations, which pose a great burden to global health and economy. Moreover, a flu pandemic arising from reassortment viruses, such as H5N1 and H1N1, raises even greater concern due to the lack of effective vaccines at the initial stage of flu outbreak. The influenza virus is the causative agent of flu infection. Currently there are four drugs in use to combat influenza infection. Amantadine and rimantadine are M2 proton channel blockers that inhibit virus uncoating; oseltamivir and zanamivir are neuraminidase (NA) inhibitors that inhibit virus release. However, recent years have witnessed a drastic increase in instances of drug resistance, and flu strains that are resistant to both classes of drugs have been reported. Thus, there is a pressing need to develop the next generation of anti-influenza drugs. Among a handful of anti-influenza drug targets, the viral fusion protein hemagglutinin (HA) is one of the most advanced. This review discusses the biological roles of HA during viral replication and highlights peptide- and small molecule–based HA inhibitors, including recent computationally designed HA binders. The text is organized into four sections based on the maturation stages of HA: inhibitors targeting the glycosylation of HA, the proteolytic activation of HA, the attachment of HA to host cell receptors, and peptide- and small molecule–based inhibitors targeting HA-mediated membrane fusion. Of particular interest are advances in the areas of developing dual inhibitors targeting both HA and NA and broad-spectrum HA inhibitors targeting both groups of HAs.
Export Options
About this article
Cite this article as:
Li F., Ma C. and Wang J., Inhibitors Targeting the Influenza Virus Hemagglutinin, Current Medicinal Chemistry 2015; 22 (11) . https://dx.doi.org/10.2174/0929867322666150227153919
DOI https://dx.doi.org/10.2174/0929867322666150227153919 |
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
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...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
![](/images/wayfinder.jpg)
- 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
-
Recent Advances in the Investigation of the Bioactive Conformation of Peptides Active at the μ-opioid Receptor. Conformational Analysis of Endomorphins
Current Topics in Medicinal Chemistry Cool the Inflamed Brain: A Novel Anti-inflammatory Strategy for the Treatment of Major Depressive Disorder
Current Neuropharmacology Alveolar Capillary Dysplasia: A Lethal Developmental Lung Malformation
Current Respiratory Medicine Reviews Approaches Towards Better Immunosuppressive Agents
Current Topics in Medicinal Chemistry Far-infrared Ray-mediated Antioxidant Potentials are Important for Attenuating Psychotoxic Disorders
Current Neuropharmacology Ansamycin Inhibitors of Hsp90: Natures Prototype for Anti-Chaperone Therapy
Current Topics in Medicinal Chemistry Engineered Soluble ACE2 Protein and SARS-CoV-2 Variants of Concern (VOCs)
Coronaviruses Platinum-Intercalator Conjugates: From DNA-Targeted Cisplatin Derivatives to Adenine Binding Complexes as Potential Modulators of Gene Regulation
Current Topics in Medicinal Chemistry The Fundamental Role of Stress Echo in Evaluating Coronary Artery Disease in Specific Patient Populations
Current Vascular Pharmacology Acetylcholinesterase: Molecular Modeling with the Whole Toolkit
Current Topics in Medicinal Chemistry Anti-Selectin Therapy for the Treatment of Inflammatory Diseases
Inflammation & Allergy - Drug Targets (Discontinued) Exploring the Nucleolar Proteome: Novel Concepts for Chaperone Trafficking and Function
Current Proteomics Recent Updates on Glucokinase Activators and Glucokinase Regulatory Protein Disrupters for the Treatment of Type 2 Diabetes Mellitus
Current Diabetes Reviews Preface
Current Analytical Chemistry The Medicinal Chemistry of Structure-based Inhibitor/Drug Design: Current Progress and Future Prospective
Current Topics in Medicinal Chemistry Computational Insights for the Discovery of Non-ATP Competitive Inhibitors of MAP Kinases
Current Pharmaceutical Design Relation between Apolipoprotein E in Alzheimer’s Disease and SARS-CoV-2 and their Treatment Strategy: A Review
CNS & Neurological Disorders - Drug Targets Healthcare Expenditures Related to BMI and Physical Activity Among Diabetic Older People: Cross-sectional Analysis of Sabe Study
Current Diabetes Reviews A Brief Study on Drug Repurposing: New Way of Boosting Drug Discovery
Letters in Drug Design & Discovery Natural Agents Modulating ACE-2: A Review of Compounds with Potential against SARS-CoV-2 Infections
Current Pharmaceutical Design