Note: Cover -- The Coronavirus Pandemic and the Future Volume 2: Virology, Epidemiology, Translational Toxicology and Therapeutics -- Dedication -- Foreword -- Preface -- Contents -- Contents -- Chapter 1 - In Silico Approaches for Drug Repurposing for SARS-CoV- 2 Infection -- 1.1 Introduction -- 1.1.1 What is Drug Repurposing -- 1.1.2 Why Drug Repurposing -- 1.1.2.1 Regulatory Considerations -- 1.1.3 Why Drug Repurposing for COVID-19? -- 1.1.4 Why In Silico Approaches for Drug Repurposing -- 1.1.4.1 Gene Profiling -- 1.1.4.2 In Vitro Screening -- 1.1.4.3 Phenotypic Screening -- 1.1.4.4 Binding Assays for Target Interactions -- 1.1.4.5 Cellular Thermal Shift Assay -- 1.1.4.6 The In Silico Effort -- 1.2 Understanding SARS-CoV- 2 from an In Silico Perspective -- 1.2.1 Structural Proteins of SARS-CoV- 2 -- 1.2.1.1 Surface Spike Protein (S-protein) -- 1.2.1.2 Nucleocapsid Protein (N-protein) -- 1.2.1.3 Envelope Protein (E-protein) -- 1.2.1.4 Membrane Protein (M-protein) -- 1.2.2 Non-structural and Accessory Proteins of SARS-CoV- 2 -- 1.2.3 Structure of SARS-CoV- 2 Proteins -- 1.3 Structure-based Approaches for Drug Repurposing -- 1.3.1 Docking Studies in the Main Protease (Mpro/3CLpro) -- 1.3.1.1 Crystal Structures Used in Docking -- 1.3.1.2 Methods or Programs Used in Docking -- 1.3.1.3 Ligands and Databases Used for Screening -- 1.3.1.4 Molecular Dynamics Programs Used -- 1.3.1.5 Duration of MD Simulation -- 1.3.1.6 Free-energy Estimation Method Used -- 1.3.1.7 Analysis of Hit Drugs from Docking -- 1.3.1.8 Some Noteworthy Studies on Mpro -- 1.3.1.8.1 Study Reporting Good Correlation of Predicted Binding Affinity with Experiments.Huynh et al. performed MD simulation of apo and ... -- 1.3.1.8.2 Studies Using Pharmacophore or Shape-based Methods for Screening of Drugs. Arun. , 1.3.1.8.3 Novel Methods of Screening. Sencanski et al. reported a novel two-step approach to identify -- 1.3.1.8.4 Studies in which Important Observations are Reported.Jin et al. reported identification of lead compounds by combining structure... -- 1.3.2 Docking Studies in RNA-dependent RNA Polymerase -- 1.3.3 Docking Studies in Papain-like Protease -- 1.3.4 Docking Studies in the Nucleocapsid Protein (N-protein) -- 1.3.5 Docking Studies in the Spike Glycoprotein (S-protein) -- 1.3.6 Docking Studies in NSP1 -- 1.3.7 Docking Studies in NSP13/Helicase -- 1.3.8 Docking Studies in NSP15/Endonucleases -- 1.3.9 Docking Studies in NSP16 -- 1.3.10 Docking in Main Protease and Spike Glycoprotein -- 1.3.11 Docking in Multiple Structural Proteins -- 1.3.12 Docking in Proteases -- 1.3.13 Docking in Multiple Targets -- 1.3.13.1 Studies Involving Large Numbers of Targets -- 1.3.13.2 Studies Involving Main Protease and Other Targets -- 1.3.13.3 Studies on Mixed Targets -- 1.3.14 Discussion and Consensus Screening Protocol from the Reviewed Literature -- 1.4 Ligand-based Approaches for Drug Repurposing -- 1.4.1 QSAR-based Approaches -- 1.4.2 Pharmacophore-based Approaches -- 1.5 Other Approaches for Drug Repurposing -- 1.5.1 Machine Learning-based Methods -- 1.5.1.1 Machine Learning Using Molecular Descriptors -- 1.5.1.2 Machine Learning Using Docking Interactions -- 1.5.2 Pharmacology-based Network Analysis Methods -- 1.5.2.1 Protein-Protein Interactions -- 1.5.2.2 Expression Profiling -- 1.6 Understanding Human Targets in COVID-19 From an In Silico Perspective -- 1.6.1 Host Proteins Involved in the SARS-CoV- 2 Life Cycle -- 1.6.2 Host Response to SARS-CoV- 2 Infection -- 1.6.2.1 SARS-CoV- 2 Induced Immune Response -- 1.6.3 Structural Information of Human Proteins in COVID-19 -- 1.7 Structure-based Approaches for Drug Repurposing Using Human Proteins. , 1.7.1 Docking Studies in Angiotensin Converting Enzyme-2 -- 1.7.1.1 Targeting the ACE-2 Receptor -- 1.7.1.2 Targeting ACE-2 and Spike Receptor -- 1.7.1.3 Targeting ACE-2 and Spike Receptor in Addition to Network-based Associations -- 1.7.2 Docking Studies in Transmembrane Protease, Serine 2 (TMPRSS2) -- 1.7.3 Docking Studies in Glucose-Regulated Protein 78 (GRP78) -- 1.7.4 Docking Studies in Furin -- 1.7.5 Docking Studies in ARDS Targets -- 1.7.5.1 TNF-­α -- 1.8 Summary of Hits from Reviewed Literature -- 1.9 Concluding Remarks -- 1.10 Executive Summary -- Author Contributions -- Acknowledgements -- References -- Chapter 2 - Vaccination and Vaccines for COVID-19 -- 2.1 Introduction -- 2.2 Vaccination in the Context of a Pandemic Outbreak -- 2.3 COVID-19 -- 2.3.1 Specific Strategies for COVID-19 -- 2.3.1.1 DNA Vaccines -- 2.3.1.2 mRNA Vaccines -- 2.3.1.3 Attenuated Vaccines -- 2.4 Mental Health Aspects of Immunization and Vaccination -- 2.5 Vaccines for COVID-19 -- 2.5.1 SARS-CoV-2 -- 2.5.2 Immune Response to SARS-CoV- 2 and Previous Coronavirus Infections -- 2.5.3 Platforms for COVID-19 Vaccine Development -- 2.5.3.1 DNA-based Vaccines -- 2.5.3.1.1 Inovio.Inovio Pharmaceuticals is an American company based in Plymouth Meeting, Pennsylvania, USA, that specializes in manufactu... -- 2.5.3.2 RNA-based Vaccines -- 2.5.3.2.1 Moderna/NIAID. Moderna is an American company based in Cambridge, Massachusetts, that has developed an mRNA -based vaccine, mRNA -1273. The mRNA vaccine -- 2.5.3.2.2 BioNTech/Fosun/Pfizer.BioNTech, a German company, together with Pfizer, an American company, have developed another mRNA- based ... -- 2.5.3.3 Non-replicating Viral Vector Vaccines -- 2.5.3.3.1 AstraZeneca/University of Oxford. The University of Oxford has formed a partnership with the -- 2.5.3.4 Inactivated Vaccines. , 2.5.3.4.1 Wuhan Institute of Biological Products/Beijing Institute of Biological Products.The above institutions and the pharmaceutical co... -- 2.5.3.4.2 Indian Vaccine Development.There are several institutions including academic/research and vaccine manufacturing companies in Ind... -- 2.5.3.5 Challenges in COVID-19 Vaccine Development -- 2.6 Executive Summary -- References -- Chapter 3 - Understanding the Emergence of SARS-CoV- 2 Viral Variants From a Genomic Perspective -- 3.1 Introduction -- 3.2 A History of Pandemics -- 3.3 Origin and Classification of SARS-CoV-2 -- 3.4 Genomic Architecture of SARS-CoV- 2 -- 3.4.1 Overview -- 3.4.2 Structural Proteins -- 3.4.3 Non-structural Proteins -- 3.5 The Emergence of SARS-CoV- 2 Variants -- 3.6 Antigenic Variations and Immune Escape Mutations -- 3.7 Leading Vaccines Across the Globe -- 3.8 Conclusion -- References -- Chapter 4 - Susceptibility and Spread of SARS-CoV- 2 in Animals -- 4.1 Introduction -- 4.2 Wild Animals -- 4.3 Laboratory Animals -- 4.4 Companion Animals -- 4.5 Farmed Animals -- 4.6 Conclusions -- References -- Chapter 5 - Profiling Some Plant-based Immunomodulatory Bioactive Compounds for COVID-19 Prophylaxis and Treatment Based on Indian Traditional Medicine -- 5.1 Introduction -- 5.2 Prevention of SARS-CoV- 19 Infection: Stage 1 -- 5.3 Incubation to Non-severe Symptomatic Phase - Stage 2 -- 5.4 Severe Respiratory Symptomatic Phase with Hyperinflammation - Stage 3 -- 5.5 Multi-organ Response to COVID-19 Infection - Stage 4 -- 5.6 Summary and Outlook -- 5.7 Executive Summary -- List of Abbreviations -- Authors' Contributions -- Declaration of Competing Interest -- Acknowledgements -- References -- Chapter 6 - The Potential Therapeutic Effects of Natural Products, Herbs, and Mushrooms Against COVID-19 -- 6.1 Origins and Pathogenesis of COVID-19. , 6.2 The Immune Profile in COVID-19Infection -- 6.3 Natural Marine Compounds as Potent Inhibitors Against SARS-CoV- 2 -- 6.4 Potential Use of Mushrooms and Herbs Against COVID-19 Infection -- 6.5 Conclusion -- References -- Chapter 7 - Application of Chinese Herbal Medicine in COVID-19 -- 7.1 Introduction -- 7.2 Representative Prescriptions -- 7.2.1 Qingfei Paidu Decoction (QFPDD, 清 排毒汤) -- 7.2.2 Huashi Baidu Formula (HSBDF, 化湿 毒方) -- 7.2.3 XuanFei Baidu Formula (XFBDF, 宣 毒方) -- 7.3 Finished Patent Medicines -- 7.3.1 Lianhua Qingwen Capsules (LH-­C, 清瘟 囊) -- 7.3.2 Jinhua Qingan Granules (JH-­G, 清感 粒) -- 7.3.3 Xuebijing Injection (XBJ, 必净注射液) -- 7.4 Other Chinese Herbs -- 7.4.1 Ephedra Herba (Ma Huang, ) -- 7.4.2 Honeysuckle (Jin Yin Hua, ) -- 7.4.3 Scutellariae (Huang Qin, ) -- 7.4.4 Glycyrrhizae Radix (Gan Cao, 甘 ) -- 7.4.5 Armeniacae Semen (Ku Xing Ren, 杏仁) -- 7.4.6 Sophorae flavescentis Radix (Ku Shen, 参) -- 7.4.7 Curcuma longa (Jiang Huang, 姜 ) -- 7.5 Conclusion -- List of Abbreviations -- References -- Chapter 8 - COVID-19 Interventional and Therapeutic Clinical Trials: Small Molecules, Interactions, Outcomes and Opportunities -- 8.1 Introduction -- 8.2 Removal-of- treatment Preventative Clinical Trials -- 8.2.1 Trial Aims -- 8.2.2 Trial Populations -- 8.2.3 Potential Therapeutics -- 8.2.4 Trial Designs -- 8.2.5 Primary Outcomes -- 8.2.6 Secondary Outcomes -- 8.2.7 Toxicities -- 8.2.8 Opportunities -- 8.3 Addition-of- treatment Preventative and/or Curative Trials -- 8.3.1 Trial Aims -- 8.3.2 Trial Populations -- 8.3.3 Potential Therapeutics -- 8.3.4 Trial Designs -- 8.3.5 Primary Outcomes -- 8.3.6 Secondary Outcomes -- 8.3.7 Toxicity -- 8.3.7.1 Population-specific Toxicity -- 8.3.7.2 Interactions -- 8.3.8 Opportunities -- 8.4 Supportive Clinical Trials -- 8.4.1 Trial Aims -- 8.4.2 Trial Populations -- 8.4.3 Potential Therapeutics. , 8.4.4 Trial Designs.

Note: Cover -- The Coronavirus Pandemic and the Future Volume 1: Virology, Epidemiology, Translational Toxicology and Therapeutics -- Dedication -- Foreword -- Preface -- Contents -- Contents -- Chapter 1 - What We Know About the Life- threatening Novel Human Coronavirus -- 1.1 Introduction -- 1.2 The Chronology of the Outbreak -- 1.3 Initial Transmission -- 1.3.1 Worldwide Spread of the Virus -- 1.4 SARS-CoV- 2 and Its Etiology -- 1.5 Classification and Grouping -- 1.5.1 Alpha- CoVs -- 1.5.2 Beta- CoVs -- 1.5.3 Gamma- CoVs -- 1.5.4 Delta- CoVs -- 1.6 Epidemiological History of Human Coronaviruses -- 1.6.1 Severe Acute Respiratory Syndrome -- 1.6.2 Middle East Respiratory Syndrome -- 1.6.3 Detailed Documentation of SARS- CoV- 2 and COVID- 19 -- 1.7 Introductory Virology and Pathophysiology of SARS- CoV- 2 -- 1.7.1 Viral Genome -- 1.7.2 Interaction of the Spike and Receptor for Entry -- 1.7.3 Genomic Differences -- 1.7.4 Pathophysiology -- 1.8 Executive Summary and Conclusions -- List of Abbreviations -- Acknowledgements -- References -- Chapter 2 - Severe Acute Respiratory Syndrome Coronavirus- 2 (SARS-CoV- 2): Structure, Lifecycle, and Replication Machinery -- 2.1 Introduction -- 2.2 Classification of Coronaviruses -- 2.3 Genomic Structure of SARS- CoV-Ł2 -- 2.4 Life Cycle of SARS- CoV- 2 -- 2.4.1 Attachment and Entry -- 2.4.2 Replicase Protein Expression -- 2.4.3 Replication and Transcription -- 2.4.4 Assembly and Release -- 2.5 SARS- CoV- 2 RNA Replication Machinery -- References -- Chapter 3 - Accumulated Epidemiological Lessons and China's COVID- 19 Response -- 3.1 Introduction -- 3.2 Accumulated Lessons from China's Response to SARS in 2003 -- 3.3 Epidemiologicial Perspective on China's COVID- 19 Response -- 3.4 China's Control and Prevention Measures in COVID- 19 -- 3.4.1 Mask- wearing and its Comforting Effect. , 3.4.2 Epidemiological Source- tracking and Slow- down of Community Transmission -- 3.5 Comparing China's Response Against SARS and COVID- 19 -- 3.6 Concluding Remarks -- 3.7 Executive Summary -- References -- Chapter 4 - Clinical Presentation, Pathophysiology and Histopathology -- 4.1 Introduction -- 4.1 Introduction -- 4.2 The Distinct Clinical Trajectory and Disease Spectrum of COVID- 19 -- 4.3 A Novel Application of Smartphone Technology -- 4.4 COVID- 19 and Comorbidities in Severe Cases -- 4.5 ARDS and its Sequelae in COVID- 19 -- 4.5.1 ARDS in COVID- 19 -- 4.5.2 Sepsis -- 4.5.3 Septic Shock -- 4.6 Pathophysiology -- 4.6.1 Mechanism of SARS-Cov- 2 Invasion into Host Cells -- 4.7 Histopathology and Disease Manifestations: Introduction -- 4.7.1 Histopathology -- 4.7.2 Pulmonary Manifestations -- 4.7.3 Cardiovascular Manifestations -- 4.7.4 Gastrointestinal Manifestations -- 4.7.5 Renal Manifestations -- 4.7.6 Neurological Manifestations -- 4.7.7 Musculocutaneous Manifestations -- 4.7.8 Hematological Manifestations -- 4.8 Executive Summary -- Acknowledgements -- References -- Chapter 5 - Evaluation of the Disease, Sample Collection and Diagnostics -- 5.1 Introduction -- 5.1.1 Symptoms of COVID- 19 -- 5.1.2 Detection of Disease Based on Symptoms -- 5.1.3 Evaluation Criteria for COVID- 19 Based on ICMR and WHO Guidelines -- 5.2 Sample Collection -- 5.2.1 Overview of Sample Collection Guidelines from the WHO -- 5.2.1.1 Nasopharyngeal or Oropharyngeal Swabs -- 5.2.1.2 Nasal Mid- turbinate Swab -- 5.2.1.3 Anterior Nares Specimen -- 5.2.1.4 Nasopharyngeal Wash/Aspirate or Nasal Wash/Aspirate -- 5.2.1.5 Bronchoalveolar Lavage, Tracheal Aspirate, Pleural Fluid, Lung Biopsy -- 5.2.1.6 Sputum (Phlegm) -- 5.2.1.7 Saliva -- 5.2.1.8 Other -- 5.3 Recent Diagnostics -- 5.3.1 Molecular Diagnostics -- 5.3.2 Laboratory Examinations (Modified from Cascella et al.17). , 5.3.3 Imaging -- 5.3.3.1 Chest X- ray -- 5.3.3.2 Chest CT -- 5.3.3.3 Lung Ultrasound -- 5.3.3.4 Scanning Techniques -- 5.3.4 Blood Parameter Levels (Laboratory Diagnostics) -- 5.3.5 Genetic Susceptibility to COVID- 19 -- 5.3.6 Importance of Real-time RT-PCR in the Detection of COVID- 19 -- 5.3.6.1 Viral Nucleic Acid Detection -- 5.3.7 Serological Assays -- 5.3.8 Enzyme- linked Immunosorbent Assay -- 5.3.9 Magnetic Chemiluminescence Enzyme Immunoassay -- 5.3.10 Colloidal Gold Immunochromatographic Assay -- 5.3.11 Lateral Flow Immunoassay -- 5.3.12 Rapid Antigen Test -- 5.3.13 Neutralization Antibody Assay -- 5.3.14 Other Useful Diagnostics for COVID- 19 -- 5.3.15 False Negatives and Positives -- 5.4 Advantages and Disadvantages of Different Diagnostic Approaches -- 5.4.1 Detection Based on Patient History -- 5.4.2 Detection of Disease Based on Symptoms -- 5.4.3 Scanning Techniques -- 5.4.3.1 CT Scan -- 5.4.3.2 Chest X- ray -- 5.4.3.3 18F- FDG PET/CT -- 5.4.4 Laboratory Serum Diagnostics (e.g. WBC, Inflammatory Markers) -- 5.4.5 Molecular Diagnosis -- 5.4.5.1 RT- PCR -- 5.4.5.2 RT- LAMP -- 5.4.5.3 Transcription- mediated Amplification -- 5.4.6 CRISPR- based Diagnosis -- 5.4.7 Serological Assays -- 5.4.7.1 ELISA -- 5.4.7.2 GICA -- 5.4.7.3 MCLIA -- 5.4.7.4 Lateral Flow Immunoassay -- 5.4.7.5 Neutralization Bioassay -- 5.4.7.6 Rapid Antigen Test -- 5.5 Executive Summary -- Acknowledgements -- References -- Chapter 6 - Therapeutic Options Initially Available for COVID- 19 Patients and Initial Clinical Trials -- 6.1 Introduction to Therapeutic Options Initially Available for COVID- 19 Patients -- 6.1.1 General Guidelines for the Treatments Provided to COVID- 19 Patients -- 6.1.2 Common Treatment Regimens Provided to COVID- 19 Patients -- 6.1.3 Medicinal Plants as Therapy for COVID- 19 -- 6.1.4 Convalescent Plasma Therapy. , 6.1.5 Mesenchymal Stem Cell-Derived Exosomes as Therapy for COVID- 19 -- 6.1.6 Other Treatment Options -- 6.1.6.1 Corticosteroids -- 6.2 Introduction to Ongoing Clinical Trials -- 6.2.1 Ongoing Trials on Various Antiviral Agents -- 6.2.2 Immunosuppressants/Immunomodulators -- 6.2.3 Current Trials on MSCs for COVID- 19 -- 6.3 Executive Summary -- Acknowledgements -- References -- Chapter 7 - Clinical Epidemiology of Coronavirus Disease 2019: Infectivity, Clinical Spectrum and Presentation, and Population Distribution -- 7.1 Introduction -- 7.2 Infection and Tests -- 7.2.1 Viral Tests -- 7.2.2 Population- based Infection Rate -- 7.2.3 Antibody Tests -- 7.3 Clinical Spectrum of COVID- 19 -- 7.3.1 Classification by Clinical Type -- 7.3.2 Asymptomatic Cases -- 7.3.3 Severe Cases and Comorbidity -- 7.3.4 Clinical and Immunological Response -- 7.4 Regional Variation in Clinical Presentation -- 7.4.1 Clinical Manifestation -- 7.4.2 Chemosensory Dysfunction -- 7.4.3 Common Symptoms -- 7.4.3.1 Asia -- 7.4.3.2 USA -- 7.4.3.3 Europe -- 7.5 Population Distribution -- 7.5.1 Pregnancy and Pregnant Women -- 7.5.2 Infants and Pediatric Patients -- 7.5.3 Asymptomatic Cases and Clinical Severity in Children -- 7.5.4 Older Adults -- 7.5.5 Sex Differences -- 7.5.6 Occupation -- 7.6 Case- fatality Rate -- 7.7 Executive Summary and Conclusions -- References -- Chapter 8 - SARS-CoV-2 Genomics and Host Cellular Susceptibility Factors of COVID- 19 -- 8.1 Introduction -- 8.2 Coronavirus and Human Diseases -- 8.2.1 Classification of Coronaviruses -- 8.2.2 Human Coronaviruses and Diseases -- 8.2.3 The Natural Origin of HCoVs -- 8.3 Genomic Structure and Genetics -- 8.3.1 Viral Genomic Structure -- 8.3.2 The Replicase Locus and Proteins -- 8.3.2.1 Nonstructural Proteins -- 8.3.2.2 Structural Proteins -- 8.3.2.3 Accessory Proteins -- 8.3.3 Genomic Mutations. , 8.4 Viral Replication -- 8.4.1 Attachment and Cell Entry -- 8.4.2 Translation and RNA Replication -- 8.4.3 Assembly and Release of Virion -- 8.5 Host Cellular Factors -- 8.5.1 ACE2 -- 8.5.2 TMPRSS2 -- 8.5.3 Furin -- 8.5.4 DPP4 -- 8.5.5 CD147 -- 8.5.6 GRP78 -- 8.5.7 Cathepsins -- 8.5.8 Ly6E -- 8.5.9 L- SIGN and DC- SIGN -- 8.5.10 Sialic Acid -- 8.5.11 Plasmin and Other Proteases -- 8.6Executive Summary -- References -- Chapter 9 - Infection and Pathogenesis of SARS-CoV- 2: an Immunological Perspective -- 9.1 Introduction -- 9.2 SARS-CoV- 2 Virology -- 9.2.1 Structure -- 9.2.2 Genome -- 9.2.3 Proteome -- 9.2.4 Mutation -- 9.2.5 Transmission -- 9.3 Pathogenesis -- 9.3.1 Attachment to the Host Cell -- 9.3.2 Penetration of SARS-CoV- 2 Inside the Host Cell -- 9.3.3 Assembly of the RTC -- 9.3.4 Genome Replication, Transcription, and Translation -- 9.3.5 Virion Assembly and Release -- 9.3.6 Incubation Period -- 9.4 Disease Progression -- 9.5 Immunology -- 9.5.1 Innate Immune Response -- 9.5.1.1 Evasion of Innate Sensing by SARS-CoV- 2 -- 9.5.1.1.1 Evasion of PRR Sensing.Coronavirus- mediated antagonism starts with the evasion of PRR recognition. The ssRNA of coronaviruses c... -- Inhibition of Signalling Cascades. As described, TLR and RLR activation induces signalling cascades, which leads to the release ... -- Inhibition of IFN-1396983920I. Based on previous studies, various mechanisms have been adopted by coronaviruses to inhibit IFN-1... -- 9.5.1.2 Imbalanced Antiviral Defense and Pro- inflammatory Cytokine Production -- 9.5.1.3 Macrophages -- Macrophage Responses to SARS-CoV- 2 Infection.Macrophages and monocytes accumulate and trigger cytokine secretion, leading to c... -- 9.5.1.4 Alveolar type II ATII Cells in the Innate Immune Response -- 9.5.1.5 Neutrophils -- 9.5.1.6 Dendritic Cells -- 9.5.1.7 Natural Killer Cells. , 9.5.1.7.1 Modification of NK Cells Upon SARS-CoV- 2 Infection.Studies on peripheral blood samples of COVID- 19 patients have shown that i.