COVID-19: From Bench to Bedside

Cover
Half Title
Title Page
Copyright Page
Dedication
Table of Contents
Preface
Acknowledgments
Editors
Contributors
Chapter 1: Coronavirus Epidemics and the Current COVID-19 Pandemic
	1.1 Epidemiology of Coronaviruses
	1.2 History and Emergence of Common Human Coronaviruses (CoVs)
	1.3 Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)
	1.4 Middle East Respiratory Syndrome Coronavirus (MERS-CoV)
	1.5 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
	1.6 Proteomic Structure of Seven Human CoVs
	1.7 The Proteomes of SARS-CoV and SARS-CoV-2
	1.8 Structural and Accessory Proteins of SARS-CoV and SARS-CoV-2
	1.9 Non-structural Proteins (NSPs) of SARS-CoV and SARS-CoV-2
	1.10 Therapeutic Targets of CoVs
	1.11 Conclusions and Future Perspectives
	Acknowledgements
	References
Chapter 2: Biology of Coronaviruses and Predicted Origin of SARS-CoV-2
	2.1 Introduction
	2.2 Biology of Coronaviruses
		2.2.1 Classification of Coronaviruses (CoVs)
		2.2.2 Genome Organization and Structure of SARS-CoV-2 Particles
		2.2.3 Life Cycle of SARS-CoV-2
	2.3 Origin of SARS-CoV-2
		2.3.1 Homology to Other Coronaviruses
		2.3.2 Scientific Evaluation of Different Theories of the Origin of SARS-CoV-2
	2.4 Conclusion
	References
Chapter 3: Therapeutic Challenges in COVID-19
	3.1 Introduction
	3.2 Summary on Antiviral COVID-19 Drugs
	3.3 Challenges in Drug Development against COVID-19
	3.4 FDA Approved Drugs
	3.5 Comorbidity and Personalized COVID-19 Drugs
	3.6 Management of COVID-19 Patients
	3.7 Conclusions
	References
Chapter 4: Prevention and Control Strategies for the COVID-19 Pandemic
	4.1 Introduction
	4.2 Pandemics Are Expected to Increase in Frequency
		4.2.1 Macro Environmental Analyses
		4.2.2 Pre-Disposal Factors at Community Level – Outbreak and Transmission
	4.3 Covid-19 Posing Different Threats and Challenges for Control Mechanisms
		4.3.1 Unique Viral Characteristics of the SARS-CoV-2
		4.3.2 Aerosol Exposure Risk and Mitigation Strategies
	4.4 Strategies for Short-Term Immediate Actions Required for Prevention and Control
		4.4.1 Physical Avoidance
		4.4.2 Lifestyles and Behavior
		4.4.3 Medical Supplements
	4.5 Strategies for Long-Term Preparedness and Readiness in Response to One Health and World Health Systems (WHO)
	4.6 Conclusion
	References
Chapter 5: Global Focus and Interdisciplinary Approaches in COVID-19 Research and Their Outcomes
	5.1 Introduction
		5.1.1 Challenges and Strategies Taken by Different Countries to Combat the Effects of the COVID-19 Pandemic
			5.1.1.1 China, Thailand, and Korea
			5.1.1.2 Australia
			5.1.1.3 United Kingdom
			5.1.1.4 Spain
			5.1.1.5 Africa
			5.1.1.6 United States
			5.1.1.7 India, Brazil, and Sweden
			5.1.1.8 Iran
			5.1.1.9 Turkey
			5.1.1.10 North Cyprus
	5.2 Focused Areas of Research
		5.2.1 Research Challenges and Recommendations
			5.2.1.1 Geriatric Care
			5.2.1.2 Medicine, Health Equity, and Management
			5.2.1.3 Psychiatry and Psychology
	5.3 Conclusions
	References
Chapter 6: The Evolution of COVID-19 Diagnostics
	6.1 Introduction
	6.2 Coronavirus Disease 2019 (COVID-19)
	6.3 Emergence and Structural Features of SARS-CoV-2
	6.4 Laboratory Diagnosis of COVID-19
		6.4.1 Computed Tomography (CT) Scans
		6.4.2 Molecular Diagnosis
			6.4.2.1 Reverse Transcription Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR)
			6.4.2.2 Reverse Transcription Loop-Mediated Isothermal Amplification (RT-LAMP)
			6.4.2.3 Transcription Mediated Amplification (TMA)
			6.4.2.4 Nicking Endonuclease Amplification Reaction (NEAR)
			6.4.2.5 Helicase-Dependent Amplification (HDA)
			6.4.2.6 Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)
			6.4.2.7 Digital Droplet PCR (ddPCR)
			6.4.2.8 Reverse Transcription – Recombinase Polymerase Amplification (RT-RPA)
			6.4.2.9 Strand Displacement Amplification (SDA)
	6.5 Serological assays
		6.5.1 Enzyme-Linked Immunosorbent Assay (ELISA)
		6.5.2 Point-of-Care Serological Assays
		6.5.3 Chemiluminescence Immunoassay
	6.6 Challenges with Existing Technologies
		6.6.1 Challenges with RT-qPCR
		6.6.2 Challenges with Isothermal Amplification-Based Assays
		6.6.3 Challenges of Antibody Tests
		6.6.4 Challenges of Antigen Tests
		6.6.5 Challenges of CT Examination
	6.7 Conclusions and Future Perspectives
	Acknowledgements
	References
Chapter 7: Drug Repurposing and Novel Antiviral Drugs for COVID-19 Management
	7.1 Introduction
	7.2 Various Repurposed Drugs and Their Characteristics Utilized against COVID-19
		7.2.1 Hydroxychloroquine (HCQ)/Azithromycin (AZ)
		7.2.2 Lopinavir/Ritonavir
		7.2.3 Umifenovir (Arbidol) versus Favipiravir
		7.2.4 Remdesivir
			7.2.4.1 Remdesvir in Children
			7.2.4.2 Remdesivir Use in Pregnant Women
		7.2.5 Molnupiravir
	7.3 Other Miscellaneous Agents in Therapy against COVID-19
		7.3.1 Interleukin Inhibitors
			7.3.1.1 Anti-Interleukin-6 Receptor Monoclonal Antibodies
				7.3.1.1.1 Sarilumab
				7.3.1.1.2 Tocilizumab (TCZ)
				7.3.1.1.3 Siltuximab
				7.3.1.1.4 Sarilumab
			7.3.1.2 Interleukin-1 Inhibitors
		7.3.2 Interferon Alone or in Combination
		7.3.3 Nitazoxanide
		7.3.4 Niclosamide
		7.3.5 Corticosteroids
		7.3.6 Convalescent Plasma
		7.3.7 Immune Modulator Trials
			7.3.7.1 Infliximab
			7.3.7.2 Abatacept
			7.3.7.3 Cenicriviroc
	7.4 Novel Strategies against COVID-19
		7.4.1 Stem Cell Therapy: Significance in COVID-19
		7.4.2 Synthetic Nano Stem Cell–Based Therapy
	7.5 Conclusions
	Acknowledgements
	References
Chapter 8: Convalescent Plasma and Antibody Therapy in COVID-19
	8.1 Introduction
	8.2 Effects of COVID-19 on the Immune System
	8.3 Immunotherapy
		8.3.1 Convalescent Plasma
			8.3.1.1 Definition, Extraction, and Applications of Plasma in Viral Infections
			8.3.1.2 Efficacy and Safety
		8.3.2 Immunoglobulins
			8.3.2.1 Non-SARS-CoV-2 Specific
			8.3.2.2 SARS-CoV-2 Specific
				8.3.2.2.1 Interleukin-6 Inhibitors
				8.3.2.2.2 Casirivimab and Imdevimab Combination
				8.3.2.2.3 Bamlanivimab
				8.3.2.2.4 Anakinra
				8.3.2.2.5 Canakinumab
				8.3.2.2.6 Emapalumab
				8.3.2.2.7 GM-CSF Inhibitors Gimsilumab, Otilimab, Namilumab, Lenzilumab, TJ003234
	8.4 Conclusions
	References
Chapter 9: Application of Stem Cell and Exosome-Based Therapy in COVID-19
	9.1 What Is COVID-19? Pathogenesis, Immune Response, and Therapeutic Strategies
	9.2 Mesenchymal Stem Cells (MSCs) and MSC-Derived Exosomes
	9.3 Characteristics of MSCs and MSC-Derived Exosomes in COVID-19: Clinical Efficacy
		9.3.1 Immunomodulation
		9.3.2 Regeneration and Repair
		9.3.3 Antimicrobial Activity
	9.4 Clinical Trials Using MSCs and MSC-Derived Exosomes
	9.5 Unique Challenges of MSCs and MSC-Derived Exosome Therapy for COVID-19
	9.6 Future Perspectives
	9.7 Conclusions
	Acknowledgments
	References
Chapter 10: Host and Pathogen-Specific Drug Targets in COVID-19
	10.1 Introduction
	10.2 ACE-2
	10.3 Other Putative Viral Receptors and Cell Entry Cofactors
	10.4 Sialic Acids
	10.5 Viral and Host Proteases
		10.5.1 SARS-CoV-2–Specific Viral Proteases
		10.5.2 Host Cell Proteases in SARS-CoV-2 Infection
	10.6 Furin and SARS-CoV-2 Entry into Host Cells
	10.7 Targeting the Viral Replication Machinery
	10.8 Conclusions
	References
Chapter 11: Computational Biology and Bioinformatics in Anti-SARS-CoV-2 Drug Development
	11.1 Challenges Associated with COVID-19 Treatment
	11.2 SARS-CoV-2 Sequencing, Data Storage, Retrieval, and Analysis
	11.3 Evolution of SARS-CoV-2
	11.4 COVID-19 and a Multi-omics Approach: Some General Considerations
	11.5 Deep Learning and Artificial Intelligence in COVID-19 Research
	11.6 Drug Discovery
		11.6.1 Search for Potential Drug Targets
			11.6.1.1 Viral Targets
			11.6.1.2 Search for Potential Host Targets of Viral Proteins
		11.6.2 Structure-Based Drug Design
			11.6.2.1 Structural Bioinformatics
		11.6.3 Search for Potential Drug Leads
			11.6.3.1 Docking and Virtual Screening
			11.6.3.2 Computational Drug Repurposing
			11.6.3.3 Phytochemicals and Natural Products
			11.6.3.4 Dietary Supplements and Functional Foods
		11.6.4 Computational Polypharmacology
		11.6.5 Target Prioritization
	11.7 Microbiome Analysis
	11.8 Vaccine Development
	11.9 Search for Biomarkers
	11.10 Conclusions
	References
Chapter 12: Nanomaterials in COVID-19 Drug Development
	12.1 Introduction
		12.1.1 Nanotechnology versus Coronavirus
	12.2 Scope of Nanotechnology Approaches
		12.2.1 Antiviral Metallic Nanomaterials
		12.2.2 Carbon-Based Antiviral Nanomaterials
		12.2.3 Small Interfering RNA
		12.2.4 CRISPR/Cas9
		12.2.5 Antiviral and Nanomaterial Delivery
			12.2.5.1 Chemical Engineering of Drug Delivery Systems
			12.2.5.2 Nanomedicine for Combination Drug Therapeutics
		12.2.6 Nano-Based Vaccine Delivery
	12.3 Conclusion and Outlook
	References
Chapter 13: Vaccine Development Strategies and the Current Status of COVID-19 Vaccines
	13.1 Introduction
	13.2 Vaccine Categories and Adjuvants
	13.3 Development Strategies of Vaccines against COVID-19
	13.4 First-Generation Vaccines
		13.4.1 Inactivated Vaccine
	13.5 Second-Generation Vaccines
		13.5.1 Protein Subunit Vaccines
		13.5.2 Viral Vector–Based Vaccines
	13.6 Third-Generation Vaccines
		13.6.1 DNA-Based Vaccines
		13.6.2 RNA-Based Vaccines
	13.7 COVID-19 Vaccines: Current Status
	13.8 COVID-19 Vaccines and Emergence of New SARS-CoV-2 Variants
	13.9 The Credibility of Concerns about COVID-19 Vaccines
	13.10 Conclusions
	References
Chapter 14: Clinical Trials of COVID-19 Therapeutics and Vaccines: History, Current Status, and Limitations
	14.1 Introduction
		14.1.1 Novel Coronavirus (SARS-CoV-2): What We Know So Far
		14.1.2 Immunopathology/Pathophysiology Underlying COVID-19 and Drug Targets
	14.2 Clinical Trials in the COVID-19 Era
		14.2.1 Immunization Strategies to Combat COVID-19 Pandemic at the Crossroads
			14.2.1.1 DNA Vaccines
			14.2.1.2 RNA Vaccines
			14.2.1.3 Viral Vector Vaccines
			14.2.1.4 Replicating Viral Vector (RVV)
			14.2.1.5 Non-Replicating Viral Vector (NRVV)
			14.2.1.6 Inactivated/Live Attenuated Virus Vaccines
				14.2.1.6.1 Inactivated Virus (IV)
				14.2.1.6.2 Live Attenuated Virus
			14.2.1.7 Recombinant Protein Subunit Vaccines
			14.2.1.8 Virus-Like Particle Vaccines
		14.2.2 Insights into Repurposing Drugs as Therapeutic Options for COVID-19
	14.3 Conclusion
	References
Chapter 15: Lessons Learned from COVID-19 and Their Implementations for Future Pandemics
	15.1 Introduction
	15.2 Arrival of SARS-CoV-2 and the COVID-19 Pandemic
	15.3 Science and Medical Support
	15.4 Internet and Computational Technologies
	15.5 Programs, Software, and Platforms
	15.6 Epidemiology, Mathematics, and Statistics
	15.7 Genomics and Bioinformatics
	15.8 Spike Mutations
	15.9 Pathology and Age
	15.10 Immunology
	15.11 Rapid Detection and Diagnostics
	15.12 COVID-19 Vaccines
	15.13 COVID-19 Drugs
	15.14 Conclusions, or Lessons Learned?
	Acknowledgements
	References
Index