UID:
almafu_9961673612302883
Format:
1 online resource (302 pages)
Edition:
First edition.
ISBN:
1-78801-685-8
,
1-83916-053-5
Series Statement:
Issn Series
Content:
Ideal for drug discovery scientists and medicinal chemists with an interest in antiviral drug discovery and development, this book provides a complete overview of the latest progress in the field, recent advances and the challenges that remain in developing these highly pathogenic agents.
Note:
Intro -- Title -- Copyright -- Contents -- Chapter 1 Overview of Antiviral Drug Discovery and Development: Viral Versus Host Targets -- 1.1 Introduction -- 1.2 Viral Targets for Antiviral Drugs -- 1.2.1 Viral Polymerases -- 1.2.2 Viral Integrase -- 1.2.3 Viral Proteases -- 1.2.4 Structural Proteins -- 1.2.5 Accessory Proteins -- 1.3 Host Targets for Antiviral Drugs -- 1.3.1 Host Chemokine Receptors -- 1.3.2 Host Glycoproteins -- 1.3.3 Host Kinases -- 1.3.4 Other Host Proteins -- 1.4 Viral Versus Host Targets -- 1.4.1 Strengths and Weaknesses of Viral Targets -- 1.4.2 Strengths and Weaknesses of Host Targets -- 1.5 Conclusion -- Conflicts of Interest -- Acknowledgements -- References -- Chapter 2 Advances in Prophylaxis and Therapy of Arenavirus Hemorrhagic Fevers -- 2.1 Introduction -- 2.2 Therapeutic Approaches Against Arenaviruses -- 2.2.1 Immunotherapeutic Approaches -- 2.2.2 Antivirals -- 2.3 Prophylaxis of Arenavirus Infections -- 2.4 Concluding Remarks -- References -- Chapter 3 Vaccines and Antiviral Developments for SARS-CoV-2 in the Emergence of the COVID-19 Pandemic1 -- 3.1 Origin of the COVID-19 Pandemic Produced by SARS-CoV-2 -- 3.2 Coronavirus and Zoonotic Risk -- 3.3 Human Coronaviruses -- 3.4 Structure and Genomic Organization of SARS-CoV-2 -- 3.5 Mechanism of Infection and Pathogenesis of SARS-CoV-2 -- 3.6 Diagnosis and Kinetics of Respiratory Infection by SARS-CoV-2 -- 3.7 The Immune Response to SARS-CoV-2 -- 3.8 Vaccine Development for COVID-19 -- 3.9 Monoclonal Antibodies Against SARS-CoV-2 for COVID-19 Treatment -- 3.10 Antiviral Development for SARS-CoV-2/COVID-19 -- References -- Chapter 4 Small-molecule and Synthetically Derived Antivirals for Ebola Virus and Other Filoviruses1 -- 4.1 Introduction -- 4.2 Broad-spectrum Nucleobase, Nucleoside, and Nucleotide Antivirals -- 4.2.1 Remdesivir -- 4.2.2 Galidesivir.
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4.2.3 Favipiravir -- 4.2.4 Other Small Molecules -- 4.3 Emerging Small-molecule and Antiviral Concepts -- 4.3.1 Kinase Inhibitors -- 4.3.2 Compounds with Unknown Mechanisms of Action -- 4.3.3 Alpha-glucosidase Inhibitors -- 4.3.4 Repurposed Drugs -- 4.3.5 β-d-N4-Hydroxycytidine -- 4.3.6 Immunomodulators -- 4.4 Nucleic Acid-based Antivirals -- 4.4.1 Antisense Therapeutics -- 4.5 Small Interfering RNAs -- 4.6 Conclusions -- Acknowledgements -- References -- Chapter 5 Antiviral Strategies for Ebola Virus and Other Filoviruses: Antibodies -- 5.1 Introduction -- 5.2 Introduction to Filoviruses -- 5.2.1 Role of Abs in Natural Infection -- 5.2.2 Role of Abs in Understanding Outbreaks -- 5.2.3 Antibody-dependent Enhancement -- 5.3 The Role of Abs Generated by Experimental Vaccines -- 5.4 Development of Antibodies for Filovirus Medical Countermeasures -- 5.4.1 EBOV mAb Countermeasures -- 5.4.2 Non-EBOV Filoviruses and pan-Ebolavirus mAbs in NHPs -- 5.4.3 Clinical Evaluation of Passive Immunization during the 2013-2016 West Africa Outbreak and the 2018-2020 DRC Outbreak -- 5.4.4 Non-recombinant mAb Alternative Passive Immunization Strategies -- 5.5 Conclusion -- Acknowledgements -- References -- Chapter 6 Vaccine Development in the Midst of Ebolavirus Disease Outbreaks -- 6.1 Introduction -- 6.2 Regulatory Considerations for the Development of an Ebolavirus Vaccine -- 6.2.1 Regulatory Strategy -- 6.2.2 Requirements for Licensure -- 6.2.3 Importance of Interactions with Regulators and Use of Expedited Pathways -- 6.2.4 Access to Vaccine Prior to Licensure -- 6.3 Ebolavirus Vaccine Manufacturing -- 6.3.1 Manufacturing History -- 6.3.2 Considerations for Manufacturing Process Development -- 6.3.3 Considerations for Analytical Test Method Development -- 6.3.4 Production Facility Design -- 6.3.5 Validation of the Manufacturing Process and Analytical Test Methods.
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6.3.6 Vaccine Supply -- 6.4 Non-clinical Immunogenicity and Efficacy Overview -- 6.4.1 Animal Models for Ebolavirus Vaccine Immunogenicity and Efficacy -- 6.4.2 Role of NHP Studies in Ebolavirus Vaccine Licensure -- 6.4.3 Immunoassay Development for NHP Studies -- 6.5 Non-clinical Safety Overview -- 6.5.1 Neurovirulence Assessment -- 6.5.2 Repeat-dose Non-clinical Toxicology Studies -- 6.5.3 Developmental and Reproductive Toxicity -- 6.5.4 Biodistribution -- 6.6 Clinical Development Program -- 6.6.1 The Collaborative Partnership -- 6.6.2 Clinical Trials Assessing Safety, Immunogenicity, and Efficacy -- 6.6.3 Manufacturing Lot Consistency -- 6.6.4 Overall Assessment of Safety -- 6.6.5 Overall Assessment of Immunogenicity -- 6.6.6 Response to Ongoing Outbreaks -- 6.7 Summary -- Conflicts of Interest -- List of Abbreviations -- Acknowledgements -- References -- Chapter 7 Remdesivir: Investigational Antiviral Drug with Activity Against Ebola and Other Emerging and Neglected Viruses -- 7.1 Major Viral Outbreak Threats on the List of WHO High-priority Diseases -- 7.2 Remdesivir and Its Mechanism of Action -- 7.3 Broad-spectrum In Vitro Antiviral Activity of Remdesivir -- 7.4 In Vivo Efficacy of Remdesivir in Animal Models -- 7.4.1 Ebola Virus -- 7.4.2 Marburg Virus -- 7.4.3 MERS Coronavirus -- 7.4.4 SARS Coronavirus -- 7.4.5 Nipah Virus -- 7.4.6 Remdesivir has a High Barrier to Resistance Emergence -- 7.5 Remdesivir Drug Products -- 7.6 Use of Remdesivir in Humans -- 7.7 Summary -- Abbreviations -- References -- Chapter 8 Therapeutics Against Nipah and Hendra Virus -- 8.1 Introduction -- 8.1.1 Henipaviruses -- 8.1.2 Hendra and Nipah Virus Outbreaks -- 8.1.3 Clinical Disease -- 8.1.4 Henipavirus Biology -- 8.2 Animal Models of Henipaviral Disease -- 8.2.1 Syrian Hamster Model -- 8.2.2 Ferret Model -- 8.2.3 African Green Monkey Model.
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8.3 Development of Therapeutics - In Vitro Screening of Compounds -- 8.4 Henipavirus Therapeutics -- 8.4.1 Virus-inactivating Compounds -- 8.4.2 Entry/Fusion Inhibitors -- 8.4.3 Inhibition of RNA Replication -- 8.4.4 Host Cell Targets -- 8.5 Discussion -- Acknowledgements -- References -- Chapter 9 Glycomimetics as Promising Inhibitors of Ebola Virus, Flavivirus and HIV Infections -- 9.1 Introduction -- 9.1.1 Glycans and C-type Lectin Receptors: A Major Interface for Sensing Friends or Foes -- 9.1.2 Viral Diversion of C-type Lectin Receptors -- 9.1.3 Designing Drugs Targeting CLRs for Viral Entry Inhibition: Challenges and Bottlenecks -- 9.2 Monovalent Ligands: The Role of Glycomimetics -- 9.3 Carbohydrate Multivalent Ligands as Pathogen Inhibitors -- 9.3.1 Dendron and Dendrimer Scaffolds -- 9.3.2 Carbon Nanoform Scaffolds -- 9.3.3 Metallic Nanoparticle Scaffolds -- 9.3.4 Miscellaneous Scaffolds -- 9.4 Conclusions -- Acknowledgements -- References -- Chapter 10 Repurposing Approved Drugs to Block Highly Pathogenic Emerging Viruses -- 10.1 Introduction to Antiviral Drug Repurposing -- 10.2 Strategies for the Identification of Approved Drugs with Repurposing Potential as Antivirals -- 10.3 Antiviral Drug Repurposing for Highly Pathogenic Emerging Viruses -- 10.3.1 Arenaviruses -- 10.3.2 Ebola Virus and Other Filoviruses -- 10.3.3 Zika Virus and West Nile Virus -- 10.3.4 Highly Pathogenic Coronaviruses -- 10.3.5 Nipah and Hendra Virus -- 10.3.6 Influenza Viruses -- 10.4 Future Perspectives -- Abbreviations -- Acknowledgements -- References -- Chapter 11 Receptors on Primary Phagocytes as Therapeutic Targets Against Highly Pathogenic Emerging Viruses -- 11.1 Introduction -- 11.2 Viral Entry into Myeloid Phagocytes -- 11.3 Glycoprotein-dependent Host Attachment Factors -- 11.4 Glycoprotein-independent Host Attachment Factors.
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11.5 Post-attachment Factors Required for Viral Infection -- 11.6 Therapeutic Agents to Block Viral Entry into Myeloid Phagocytes -- 11.7 Concluding Remarks -- Author Contribution -- Competing Interest -- Acknowledgements -- References -- Subject Index.
Additional Edition:
ISBN 1-78801-564-9
Language:
English
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