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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