Viral Infections and Antiviral Therapies

Front Cover
Viral Infections and Antiviral Therapies
Copyright Page
Contents
List of contributors
Preface
I. Introduction
1 Introduction to antiviral therapy
1.1 Introduction
1.2 Virus replication cycle
1.3 Virus transmission and types of viral infections
1.4 Antiviral agents
1.4.1 Antiherpes virus agents
1.4.2 Anti-HIV agents
1.4.3 Antiviral drugs used for the treatment of hepatitis
1.4.4 Anti-influenza agents
1.4.5 Antiviral agents against flavivirus
1.5 Antiviral agents obtained from plant sources
1.6 Antiviral vaccines
1.7 Immunotherapy and role of nutraceuticals in viral infection
1.8 Challenges in the development of antiviral agents
1.9 Conclusion
References
Further reading
II. Viral infections and transmission
2 Emerging viral diseases
2.1 The everchanging landscape of infectious diseases
2.2 Causes of emergence
2.3 Ebola virus
2.4 Dengue virus
2.5 Chikungunya virus
2.6 West Nile virus
2.7 Zika virus
2.8 Yellow fever virus
2.9 Nipah virus
2.10 Influenza virus
2.11 Corona viruses
2.12 Prevention and control
2.13 The global response
2.14 Conclusions and the way forward
References
3 Evolution and transmission of viruses
3.1 Introduction
3.2 Viral Evolution
3.2.1 Genetic basis of virus evolution
3.2.1.1 Mutation
3.2.1.2 Genetic recombination
3.2.1.3 Genetic reactivation
3.2.1.4 Viral interference
3.2.2 Ecological basis of virus evolution
3.2.2.1 Reproductive rate and antigenic diversity
3.2.2.2 Herd immunity and selective pressure
3.2.2.3 The spillover event
3.3 Transmission
3.4 Modes of transmission of viruses
3.4.1 Respiratory tract
3.4.2 Gastrointestinal tract
3.4.3 Genital tract
3.4.4 Skin
3.4.5 Eyes
3.4.6 Placenta
3.4.7 Transplants
3.5 Conclusion
References
Further reading
4 Mode of viral infections and transmissions
4.1 Introduction
4.2 Epidemiological triad and viral infection
4.3 Transmission of infection and clinical presentation
4.4 Modes of transmission of viral infection
4.5 Conclusion
4.6 Conflict of interest
References
5 Transmission and intervention dynamics of SARS-CoV-2
5.1 Introduction
5.2 Coronaviruses
5.3 Transmission characteristics of SARS-CoV-2
5.4 Intervention, strategies, and impacts
5.5 Summary
References
6 Sexually transmitted viral infections
6.1 Introduction
6.2 Human papilloma virus (HPV infection)
6.3 Effects of human papilloma virus on pregnancy and the neonate [2,4]
6.4 Herpes simplex virus type 1 and 2
6.5 Human T-cell lymphotropic virus infection
6.6 Hepatitis A (HAV infection)
6.7 Hepatitis B (HBV infection)
6.8 Hepatitis C (HCV infection)
6.9 Prevention of sexually transmitted viral infections
6.9.1 Cognizance
6.9.2 Affective
6.9.3 Psychomotor
6.10 Health education
6.10.1 Individual level
6.10.2 Mass level
6.11 Conclusion
References
7 Testing viral infections
7.1 Introduction
7.2 The purpose of laboratory diagnosis of viral infections
7.3 Sample collection, packaging, and transport
7.4 Type of specimen
7.5 Labeling/requisition form has the following information
7.6 Methods in diagnostic virology
7.6.1 Virus isolation
7.6.1.1 Tissue culture
7.6.1.1.1 Preparation of the cell lines
7.6.1.1.2 Types of cell lines
7.6.1.1.3 Cytopathic effect
7.6.1.2 Animal inoculation
7.6.1.3 Egg inoculation
7.6.2 Assays measuring viral infectivity
7.6.2.1 Quantitative assays
7.6.2.2 Quantal assays
7.6.2.3 Hemagglutination
7.6.3 Direct microscopy
7.6.3.1 Electron microscopy
7.6.3.2 Fluorescence microscopy
7.6.3.3 Immunoperoxidase staining
7.6.4 Histology/cytology
7.6.5 Detection of viral antigens and antibody (serology)
7.6.5.1 Immunochromatography
7.6.5.2 Enzyme-linked immunosorbent assay
7.6.5.3 Neutralization assays
7.6.5.4 Latex particle agglutination
7.6.5.5 Western blotting
7.6.5.5.1 Applications of serology
7.6.6 Molecular techniques
7.6.6.1 Detection of viral nucleic acids
7.6.6.1.1 Nucleic acid hybridization
7.6.6.1.2 Polymerase chain reaction
7.6.6.2 Microarray technologies
7.6.6.3 Sequencing
7.6.6.3.1 Sanger sequencing
7.6.6.3.2 Next-generation sequencing
7.6.6.3.3 Third-generation sequencing
7.6.6.3.4 Fourth-generation sequencing
7.7 Conclusion
Further reading
8 Electron microscopic methods for virus diagnosis
Abbreviations
8.1 Introduction
8.1.1 Electron microscopy as a diagnostic tool
8.1.2 Electron microscopy in plant and animal virus diagnosis
8.1.3 Dengue virus
8.1.4 Rabies virus
8.1.5 Ebola virus
8.1.5.1 Cucumber mosaic virus
8.1.5.2 Tobacco mosaic virus
8.1.5.3 Tomato spotted wilt virus
8.1.5.4 Tomato yellow leaf curl virus
8.1.5.5 Potato virus X and potato virus Y
8.2 Other plant viruses
8.2.1 Sample preparation for electron microscopic analysis
8.2.2 Scanning and transmission electron microscopy: structure and functions
8.2.3 Electron generator
8.2.4 Electron lenses
8.2.5 Signals and detectors
8.2.6 Vacuum system
8.3 Concluding remarks and future trends
References
III. Antiviral agents and therapeutics
9 Virotherapy
9.1 Introduction
9.2 Oncolytic virus in common cancers and molecular changes observed during infection
9.3 Breast cancer
9.4 Lung cancer
9.5 Bladder and endometrial cancer
9.6 Renal and prostate cancer
9.7 Leukemia
9.8 Hepatocellular carcinoma
9.9 Melanoma
9.10 Brain cancer
9.11 Oncolytic viruses under clinical trial
9.12 Future directions
Softwares used for images
Author contribution
Conflicts of interest
Funding statement
Authors statement
References
10 Challenges in designing antiviral agents
10.1 Introduction
10.2 Strategies for the design of antiviral agents
10.2.1 Virus attachment (or adsorption) inhibitors
10.2.2 Virus entry inhibitors
10.2.3 Viral polymerase inhibitors
10.2.4 Viral protease inhibitors
10.3 Biggest challenging viruses
10.3.1 Herpes viruses (HSV-1 and HSV-2)
10.3.1.1 Promising compounds against herpes simplex virus
10.3.2 Respiratory viruses
10.3.2.1 Influenza A and B
10.3.2.1.1 Adamantane analogs and their limitations in drug design
10.3.2.1.2 Neuraminidase inhibitors against influenza-A and influenza-B
10.3.2.2 Severe-acute respiratory syndrome coronavirus-2
10.3.2.2.1 Nucleoside analogs against severe-acute respiratory syndrome coronavirus-2
10.3.3 Human immunodeficiency virus
10.3.3.1 The virus and its some limitations in drug design
10.3.3.2 Reverse transcriptase inhibitors
10.3.3.3 Anti-HIV protease inhibitors
10.3.4 Emerging viruses
10.3.4.1 Hepatitis B virus
10.3.4.1.1 Some limitations and challenges to identifying new anti-hepatitis B virus drugs
10.3.4.1.2 Promising compounds targeting anti-hepatitis B virus activity
10.3.4.2 Dengue virus
10.3.4.2.1 Promising compounds discovered against dengue virus
10.3.4.2.2 Promising active compounds against dengue virus
10.3.5 Hemorrhagic fever viruses
10.3.5.1 Ebola virus
10.3.5.1.1 Some limitations to overcome in drug discovery targeting Ebola virus
10.3.5.1.2 Promising compounds against Ebola virus
10.3.5.2 Lassa virus
10.3.5.2.1 Promising compounds against Lassa virus
10.4 New trends, challenges, and opportunities
10.5 Conclusions
Conflict of interest
Consent for publication
References
11 Anti-influenza agents
11.1 Introduction
11.2 The virus
11.2.1 Virion structure
11.2.2 Viral genes and viral proteins
11.2.3 Life cycle of influenza virus
11.3 Anti-influenza agents
11.3.1 Regulatory authority-approved anti-influenza agents
11.3.1.1 Class I. Matrix protein 2 ion channel inhibitor
11.3.1.1.1 Amantadine
11.3.1.1.2 Rimantadine
11.3.1.2 Class II. Neuraminidase inhibitors
11.3.1.2.1 Zanamivir
11.3.1.2.2 Oseltamivir
11.3.1.2.3 Peramivir
11.3.1.2.4 Laninamivir
11.3.1.3 Class III. RNA-dependent RNA polymerase inhibitors
11.3.1.4 Class IV. Polymerase acidic protein inhibitor
11.3.1.5 Hemagglutinin inhibitor
11.3.2 Anti-influenza agents under development
11.3.2.1 Anti-influenza agents under clinical trials
11.3.2.1.1 Nitazoxanide
11.3.2.1.2 DAS181
11.3.2.1.3 AL-794
11.3.2.2 Anti-influenza agents under basic research
11.3.3 Anti-influenza agents from traditional plants
11.4 Conclusion
References
12 Anti-herpes virus agents
12.1 Herpes simplex: a DNA virus
12.2 Clinical administration of viral infection
12.2.1 Acyclovir
12.2.1.1 Mechanism of action
12.3 Disadvantages of acyclovir
12.3.1 Famciclovir/penciclovir
12.3.1.1 Mechanism of action
12.3.2 Ganciclovir
12.3.2.1 Mechanism of action
12.3.3 Foscarnet
12.3.3.1 Mechanism of action
12.3.3.2 Cidofovir
12.3.3.2.1 Mechanism of action
12.3.3.3 Fomivirsen
12.3.3.4 Mechanism of action
12.3.3.5 Trifluridine
12.3.3.6 Mechanism of action
12.3.4 Indoxuridine
12.3.4.1 Mechanism of action
12.4 Ethnomedicine: a gift of God to solve the problems of synthetic drugs
12.5 Mode of action of plant-derived anti-herpes virus agents
12.6 Inhibition of virus replication
12.7 Inhibition of herpes simplex viruses by immunomodulation
12.8 Interference with virus release
12.9 Inhibition of herpes simplex viruses by autophagy
12.10 Inhibition of viral entry into the host cell
12.11 Conclusion
References
13 Antiretroviral therapy
13.1 Introduction
13.2 Formulation of antiretroviral treatment
13.3 General principles for antiretroviral therapy initiation
13.4 Considerations before initiation of antiretroviral therapy
13.5 Monitoring on the patient on antiretroviral therapy
13.6 Immune reconstitution inflammatory syndrome
13.7 Antiretroviral failure
13.8 Drug interaction
13.9 Antiretroviral drug resistance
13.10 Preexposure prophylaxis
13.11 Postexposure prophylaxis
13.12 Prevention of mother child transmission
References
14 Rotavirus and antirotaviral therapeutics: trends and advances
14.1 Introduction
14.2 Supportive/symptomatic therapies
14.2.1 Fluid therapy
14.2.2 Antibiotic treatment
14.3 Antiviral drugs/mimetics
14.3.1 Interference in attachment and entry of virus into host cells
14.3.2 Interefrence in host cell lipid metabolic pathways
14.3.3 Inhibition of viroplasm formation
14.3.4 Interefrence in viral RNA and protein synthesis
14.3.5 Targeting RNA interference pathway
14.4 Passive immunotherapy
14.5 Immunotherapeutics
14.6 Immunomodulators
14.7 Cytokines-based therapeutics
14.8 Toll-like receptors-based therapeutics
14.9 Herbal/medicinal plants
14.10 Probiotics
14.11 Advances in drug delivery: nanotechnology-based approach
14.12 Neutraceuticals
14.12.1 Milk proteins
14.12.2 Cholesterol
14.12.3 L-isoleucine
14.12.4 Vitamin D3
14.12.5 Oligosaccharides
14.13 Antioxidants
14.14 Combinational therapy
14.15 Other potential therapeutic approaches
14.16 Conclusion and future prospects
References
15 Current therapeutic strategies and novel antiviral compounds for the treatment of nonpolio enteroviruses
15.1 Introduction
15.2 Structure and life cycle
15.3 Clinical manifestations
15.4 Antiviral agents
15.4.1 Capsid inhibitors
15.4.2 Inhibitors of nonstructural viral components
15.4.3 Nucleoside analogs
15.4.4 Inhibition of host cellular components
15.4.5 Other compounds
15.5 Advances in vaccine development for HFMD and EV-D68 infections
15.5.1 Inactivated whole vaccines
15.5.2 Recombinant subunit vaccines
15.5.3 Multivalent and chimeric vaccines
15.5.4 Vaccine candidates for enterovirus D68
15.5.5 Live attenuated vaccines
15.6 Conclusion
References
16 Antiviral agents against flaviviruses
16.1 Introduction
16.2 Flaviviruses
16.2.1 Flavivirus genus
16.2.2 Flaviviruses proteins
16.2.2.1 Structural proteins
16.2.2.2 Nonstructural proteins
16.3 Why develop novel antiviral drugs?
16.4 Recent advances in inhibitors targeting flaviviruses
16.4.1 Hepatitis C virus
16.4.2 Dengue and Zika viruses
16.4.3 Japanese encephalitis virus
16.4.4 West Nile virus
16.4.5 Tick-born encephalitis virus
16.4.6 Yellow fever virus
16.5 Conclusion
Conflict of interest
References
17 Pathophysiology of HIV and strategies to eliminate AIDS as a public health threat
17.1 Background
17.1.1 Human immunodeficiency virus
17.1.2 Acquired immunodeficiency syndrome
17.1.3 Epidemiology
17.1.4 Transmission and establishment of infection
17.1.5 Human immunodeficiency virus life cycle
17.1.6 Physiopathogenesis
17.1.6.1 CD4+ T cell depletion
17.1.6.2 Immunoactivation
17.1.6.3 Depletion of intestinal lymphoid tissue
17.1.6.4 Metabolic alterations
17.1.7 Response to human immunodeficiency virus infection
17.1.7.1 Humoral response
17.1.7.2 Cellular response
17.1.7.3 Viral escape mechanism
17.2 Natural history of human immunodeficiency virus infection
17.2.1 Transmission route
17.2.2 Manifestation of acute human immunodeficiency virus infection
17.2.3 Laboratory diagnosis
17.2.4 Antiretroviral treatment
17.3 Strategies to eliminate human immunodeficiency virus as a public health threat
17.3.1 Community participation
17.3.2 Expansion of testing
17.3.3 Preexposure prophylaxis
17.3.4 Antiretroviral treatment
17.3.5 Human immunodeficiency virus cure
References
18 Herbal drugs to combat viruses
18.1 Introduction
18.2 Phytochemicals preventing attachment of virus to host cell
18.3 Phytochemicals preventing penetration and uncoating of viruses
18.4 Phytochemicals inhibiting replication of viral nucleic acids
18.5 Phytochemicals preventing assembly and release of virus
References
19 Strategies for delivery of antiviral agents
19.1 Introduction
19.2 Classes of antiviral drugs
19.2.1 Antihuman immunodeficiency virus drugs
19.2.2 Antiviral drugs used for the treatment of herpes
19.2.3 Antihepatitis drugs
19.2.4 Antiviral drugs for the treatment of Ebola
19.2.5 Antiviral drugs used for the treatment of human papillomavirus
19.2.6 Viral pneumonia antiviral drugs
19.2.7 Antiviral drugs used for the treatment of respiratory infection
19.3 The general mechanism of viral infections
19.4 Challenges in the treatment of viral infections
19.5 Combination therapy (fixed-dose combination) for the treatment of viral infections
19.6 Hybrid compounds designed for the treatment of viral infections
19.6.1 Anti-human immunodeficiency virus hybrids
19.6.2 Anti-herpes simplex virus hybrids
19.6.3 Anti-hepatitis
19.6.4 Hybrid compounds with anti-COVID-19
19.6.5 Ebola
19.6.6 Human papilloma virus
19.6.7 Middle East respiratory syndrome
19.7 Lipid-based drug delivery systems
19.7.1 Emulsion
19.7.2 Liposomes
19.7.3 Solid lipid nanoparticles
19.8 Polymer-based drug delivery system for viral infections
19.8.1 Micelles
19.8.1.1 Micelles for loaded with antihuman immunodeficiency virus drugs
19.8.1.2 Micelles for herpes management
19.8.1.3 Micelles for hepatitis treatment
19.8.1.4 Micelles for the treatment of Human papilloma virus
19.8.1.5 Micelles for the treatment of respiratory infections (common cold, COVID-19, and Middle East respiratory syndrome)
19.8.2 Dendrimers
19.8.2.1 Dendrimers for the treatment of human immunodeficiency virus
19.8.2.2 Dendrimers for herpes treatment
19.8.2.3 Dendrimers for hepatitis treatment
19.8.2.4 Dendrimers for Ebola treatment
19.8.2.5 Dendrimers for Human papilloma virus treatment
19.8.2.6 Dendrimers efficacy against respiratory infections: COVID-19 and Middle East respiratory syndrome
19.8.3 Polymer-drug conjugates
19.8.3.1 Polymer-drug conjugates for human immunodeficiency virus treatment
19.8.3.2 Polymer-drug conjugates for herpes and hepatitis treatment
19.8.3.3 Polymer-drug conjugates for COVID-19 treatment
19.8.4 Nanocapsules
19.8.4.1 Nanocapsules for human immunodeficiency virus treatment
19.8.4.2 Nanocapsules for hepatitis treatment
19.8.5 Polymeric nanoparticles and nanospheres
19.8.5.1 Nanoparticles and nanospheres for human immunodeficiency virus treatment
19.8.5.2 Polymeric nanoparticles and nanospheres for the treatment of herpes
19.8.5.3 Polymeric nanoparticles and nanospheres for the treatment of hepatitis
19.8.5.4 Polymeric nanoparticles and nanospheres for COVID-19 treatment
19.8.6 Hydrogels and nanogels
19.8.6.1 Hydrogels and nanogels for human immunodeficiency virus treatment
19.8.6.2 Hydrogels and nanogels for herpes treatment
19.8.6.3 Hydrogels and nanogels for hepatitis and Human papilloma virus treatment
19.8.6.4 Hydrogels and nanogels for Ebola treatment
19.9 Conclusion and future perspective
References
20 Nanovesicles for delivery of antiviral agents
Abbreviation
20.1 Introduction
20.2 Overcoming the challenges of traditional delivery of antiviral agents
20.3 Nanovesicles
20.3.1 Nanovesicles composition
20.3.2 Nanovesicles fabrication methods
20.3.2.1 Thin film hydration method
20.3.2.2 Reverse phase evaporation method
20.3.2.3 Detergent removal by dialysis method
20.3.3 Nanovesicles characterization
20.3.4 Nanovesicles applications in nanomedicine
20.3.4.1 Liposomes
20.3.4.2 Niosomes
20.3.4.3 Transfersomes
20.3.4.4 Ethosomes
20.3.5 Challenges of nanovesicles for nanomedicine applications
20.4 Nanovesicles and biomimetic nanovesicles for delivery of antiviral agents
20.4.1 Liposomes for delivery of antiviral agents
20.4.2 Niosomes for delivery of antiviral agents
20.4.3 Ethosomes for delivery of antiviral agents
20.4.4 Biomimetic nanovesicles for delivery of antiviral agents
20.4.5 Exosomes for delivery of antiviral agents
20.5 Conclusion and future prospects
References
21 Antiviral biomaterials
21.1 Introduction to antiviral biomaterials
21.1.1 Types of biomaterials
21.1.1.1 Hydrogels
21.1.1.2 Cryogels
21.1.1.3 Nanoparticles
21.2 Mechanism of action
21.2.1 Structure of virus
21.2.2 Action mechanism of biomaterials
21.2.2.1 Physical adsorption of viruses
21.2.2.2 Entry inhibitors
21.2.2.3 Induction of irreversible viral deformation
21.2.2.4 Interference in nucleic acid replication
21.2.2.5 Blockage of virion release from infected cells
21.3 Applications of antiviral biomaterials
21.3.1 Diagnostics
21.3.1.1 Nucleic acid testing
21.3.1.2 Point-of-care tests
21.3.2 Antiviral therapies
21.3.2.1 Drug delivery
21.3.2.2 Vaccination
21.3.3 Other antiviral strategies
21.3.3.1 Surface inactivation
21.3.3.2 Viral filtration
21.4 Recent advancements
21.4.1 Biomaterials and nanotechnology
21.4.1.1 Nanoparticles
21.4.1.2 Nanodecoy
21.4.1.3 Nanosponges
21.4.2 Adjuvants
21.4.3 Challenges associated with antiviral biomaterials
21.5 Summary/conclusion
Conflict of interest
References
22 Antiviral biomolecules from marine inhabitants
22.1 Introduction
22.2 Marine polysaccharides
22.2.1 Chitin, chitosan, and their derivatives
22.2.2 Carrageenan
22.2.3 Alginates
22.2.4 Fucans, fucoidans
22.3 Other marine polysaccharides as antiviral biomaterials
22.4 Marine peptides as antiviral biomaterials
22.5 Conclusion
References
23 Plant polysaccharides as antiviral agents
23.1 Introduction
23.2 Antiviral mechanisms in polysaccharides
23.2.1 Directly interacting with virus
23.2.2 Inhibiting virus adsorption and invasion
23.2.3 Inhibiting viral transcription and replication
23.2.4 Activating host antiviral immunomodulatory system
23.3 Plant polysaccharides
23.4 Antiviral activities of plant polysaccharides
23.4.1 Effect on hepatitis viruses
23.4.2 Effect on influenza viruses
23.4.3 Effect on herpes simplex viruses
23.4.4 Effect on human immunodeficiency viruses
23.4.5 Effect on enterovirus
23.4.6 Effect of Newcastle disease virus
23.4.7 Effect on rotavirus
23.4.8 Effect on other viruses
23.5 Plant polysaccharide adjuvant for COVID-19 vaccine
23.6 Conclusions and future perspectives
References
24 Antiviral peptides against dengue virus
24.1 Introduction
24.1.1 Dengue virus
24.1.2 The life cycle of dengue virus
24.1.3 Antiviral peptides as potential therapeutic agents against dengue virus
24.2 Antiviral peptides targeting dengue virus
24.2.1 Peptides from animal origins
24.2.2 Peptides from plant origins
24.2.3 Synthetic peptides
24.2.4 Recombinant peptides
24.3 Strategies to identify and develop antiviral peptides against dengue virus
24.3.1 Biopanning of phage display peptide libraries
24.3.2 Structure-based design of antiviral peptides
24.3.2.1 Molecular docking
24.3.2.2 De novo design of antiviral peptides
24.3.2.3 Rational design of antiviral peptides
24.4 Direct interactions between antiviral peptides with host cell receptors and enzymes
24.4.1 Interactions between antiviral peptides and dengue virus host cell receptors
24.4.2 Interactions between antiviral peptides and dengue virus proteases
24.4.3 Interactions between antiviral peptides and dengue virus methyltransferases
24.5 Advantages of peptides as antiviral agents
24.6 Limitations of peptides
24.6.1 Chemical modifications to overcome peptide limitations
24.6.2 Delivery of peptides using nanomaterials
24.7 Conclusion
Disclosure of interest
References
25 mRNA vaccines for COVID-19
25.1 Introduction
25.2 General advantages associated with messenger RNA vaccines
25.3 General concerns associated with messenger RNA vaccines
25.4 The target viral antigen selection for the COVID-19 messenger RNA vaccines
25.5 Development of the COVID-19 messenger RNA vaccines
25.5.1 The characteristic features of the sequence of the Pfizer-BioNTech (BNT162b2) mRNA vaccine
25.6 Lipid nanoparticles-mediated delivery of the COVID-19 messenger RNA vaccines
25.6.1 Composition and functional roles of the components of the LNP delivery system
25.6.1.1 The cationic or ionizable lipids
25.6.1.2 Phospholipids
25.6.1.3 Cholesterol
25.6.1.4 Polyethylene glycol lipids
25.7 Vaccine uptake at the injection site and translation at the cellular level
25.8 Immune responses induced by COVID-19 messenger RNA vaccines
25.8.1 Humoral immunity and germinal center reactions
25.8.2 Innate immune response induced by the messenger RNA vaccines
25.9 Conclusion
References
26 Immunotherapy as an emerging and promising tool against viral infections
Abbreviation
26.1 Introduction
26.2 Vaccines
26.3 Antibody-based therapies
26.4 Chimeric antigen receptor T cells immunotherapy
26.4.1 Checkpoint inhibition therapy
26.5 Defensin therapy
References
27 Role of nutraceuticals as immunomodulators to combat viruses
27.1 Introduction
27.2 Immunity and its classification
27.2.1 Innate immunity
27.2.2 Adaptive immunity
27.2.2.1 The cells involved in adaptive immune responses are
27.2.2.1.1 T cells and antigen-presenting cells
27.2.2.1.2 T helper cells
27.2.2.1.3 B cells
27.2.2.1.4 Natural killer cells
27.2.2.2 Mediators in immune response
27.2.2.2.1 Cytokines
27.2.2.2.2 Chemokines
27.2.2.2.3 Interferons
27.2.2.2.4 Complement activation
27.2.2.2.5 Oxidative stress
27.3 Virus evasion of the host immune system
27.3.1 Mechanism of evasion of major histocompatibility complex class I and cytotoxic T lymphocytes
27.3.2 Molecular mimicry and immune evasion
27.3.3 Complement evasion
27.4 Mechanism of action of nutraceuticals
27.4.1 Inhibiting NOX-2
27.4.2 Enhancing MAVS
27.4.3 Antioxidant potency
27.5 Nutraceuticals
27.5.1 Definition
27.5.2 Classification of nutraceuticals
27.5.2.1 Dietary fiber
27.5.2.1.1 Probiotics
27.5.2.1.2 Prebiotics
27.5.2.2 Polyunsaturated fatty acids
27.5.2.3 Antioxidants
27.5.2.4 Egg as a functional food
27.5.2.5 Nutraceuticals from microbes
27.5.2.6 Citrus fruits
27.5.2.7 Nutraceuticals from marine organisms
27.5.2.8 Herbs and spices
27.5.2.8.1 Capsicum
27.5.2.8.2 Resveratrol
27.5.2.8.3 Glycyrrhizin
27.5.2.8.4 Black caraway
27.5.2.8.5 Garlic
27.5.2.8.6 Cinnamon
27.5.2.8.7 Black pepper
27.5.2.8.8 Moringa
27.5.2.8.9 Quercetin
27.5.2.9 Mushrooms
27.5.2.10 Vitamins and minerals
27.5.2.10.1 Vitamin C
27.5.2.10.2 Vitamin D
27.5.2.10.3 Vitamin A
27.5.2.10.4 Zinc
27.5.3 Other nutraceutical sources with antiviral properties
27.5.3.1 Honey
27.5.3.2 Bee propolis
27.5.3.3 Seed storage proteins
27.5.3.3.1 Glutenins
27.5.3.3.2 Prolamins
27.5.3.3.3 Mechanisms of antiviral activity of seed storage proteins
27.5.3.4 Yogurt and lactoferrin
27.6 Conclusion
References
IV. Others
28 In vitro and in vivo approaches for evaluating antiviral efficacy
28.1 Introduction
28.1.1 Antiviral activity
28.2 In vitro approaches
28.2.1 Cell-based assays
28.2.1.1 Antiviral assay by cytopathic effect
28.2.1.2 Plaque reduction assay
28.2.1.3 Hemagglutination inhibition assay
28.2.1.4 Cell-based immunodetection assay
28.2.2 Biochemical assays
28.2.3 Neuraminidase inhibition assay
28.3 In vivo assays approaches
28.3.1 Coronavirus (SARS-CoV-2)
28.3.2 Herpes virus
28.3.3 Influenza virus
28.3.4 Human immunodeficiency virus
28.3.5 Hepatitis B virus
28.4 Conclusion
References
29 Clinical Trials and Regulatory considerations of Antiviral agents
Abbreviations
29.1 Introduction
29.2 Classification of antiviral agents
29.3 Clinical trials and Food and Drug Administration in the development of antiviral agents
29.4 The US regulator (Food and Drug Administration)
29.5 Applications submitted to division of antiviral products (US FDA)
29.5.1 Investigational new drug application
29.5.2 New drug application
29.5.3 Abbreviated new drug application
29.6 Clinical trials and Food and Drug Administration recommendations for antiherpes viral drugs
29.6.1 Drugs against cytomegalo viral infections
29.6.2 Drugs against herpes simplex virus infections
29.6.3 Drugs against Kaposis sarcoma infections
29.6.4 Drugs against Epstein–Barr viral infections
29.7 Clinical trials and Food and Drug Administration recommendations for anti-HIV drugs
29.7.1 Doravirine
29.7.2 Dolutegravir
29.8 Clinical trials and Food and Drug Administration recommendations for Antiinfluenza viral drugs
29.8.1 Baloxavir marboxil
29.8.2 Oseltamivir
29.8.3 ARMS-1 (A patented formulation)
29.8.4 Cocoa-based plant extracts
29.9 Clinical trials and Food and Drug Administration recommendations for Antihepatitis viral drugs
29.9.1 Drugs against hepatitis B infections
29.9.2 Drugs against hepatitis C infections
29.9.3 Drugs against hepatitis D infections
29.10 Clinical trials of herbal molecules as antiviral agents
29.11 Conclusions and future prospects
References
30 Future perspectives of antiviral therapy
30.1 Introduction
30.2 General classification of antiviral drugs
30.2.1 Direct-acting antiviral compounds
30.2.2 Host acting antiviral compounds
30.2.3 Small molecules and large molecules
30.2.4 Mono and combination drug therapy
30.2.5 Polymerase inhibitors
30.2.6 Reverse transcriptase inhibitors
30.2.7 Protease inhibitors
30.2.8 Integrase inhibitors
30.2.9 Nonstructural protein 5A inhibitors
30.3 Problems and limitations in antiviral drugs
30.3.1 Resistance shown after long-term use of antivirals
30.3.2 Toxicity and immunosupression
30.3.3 Viral latency
30.3.4 Time-consuming, tedious, and associated with risks
30.4 Modern perspectives in the development approaches of antivirals
30.4.1 The antisense approach
30.4.2 The aptameric approach
30.4.3 The ribozyme approach
30.4.4 The CRISPR/Cas9 approach
30.4.5 The technological shift in the omics era
30.5 Conclusion
References
Index
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