Drug Repurposing for Emerging Infectious Diseases and Cancer

Preface
Contents
Editors and Contributors
Chapter 1: Drug Repurposing: An Advance Way to Traditional Drug Discovery
	1.1 Introduction
	1.2 Rationale of Drug Repurposing
	1.3 Role of Drug Repurposing in Conventional Pharmaceutical Market
	1.4 Roadmap to Modern Drug Repurposing
	1.5 Drug Repurposing Strategies and Approaches
		1.5.1 Computational Approaches
		1.5.2 Experimental Approaches
	1.6 Opportunity and Challenges in Drug Repurposing
	1.7 Conclusion
	References
Chapter 2: Drug Polypharmacology Toward Drug Repurposing
	2.1 Drug Pharmacology
	2.2 Drug Repurposing
	2.3 Need for Drug Repurposing
	2.4 Challenges of Drug Repurposing
	2.5 Different Strategies of Drug Repurposing
	2.6 Methodology for Drug Repurposing
		2.6.1 Virtual Screening
		2.6.2 Structure Prediction of Target
	2.7 Chemical Composition of Drug
	2.8 Prediction of Protein Binding Site
	2.9 Successful Example of Drug Repurposing
	References
Chapter 3: Pharmacovigilance-Based Drug Repurposing
	3.1 Drug Development and Pharmacovigilance
		3.1.1 Need for Pharmacovigilance
	3.2 Pharmacovigilance and Drug Repurposing
		3.2.1 Serendipity
		3.2.2 Signature Matching
		3.2.3 Mechanistic Profiling
		3.2.4 Inverse Signals
			3.2.4.1 Signal
				3.2.4.1.1 Inverse Signal
	3.3 The Process of Drug Repurposing
		3.3.1 Present Scenario
			3.3.1.1 Alzheimer´s Disease
			3.3.1.2 Raynaud´s Phenomenon (RP)
			3.3.1.3 COVID-19
	3.4 Future Perspectives
	Further Reading
Chapter 4: In Silico Analysis of Cellular Interactors of PQBP1 for Potential Drug Repurposing
	4.1 Introduction
	4.2 Material and Methods
	4.3 Results and Discussion
	References
Chapter 5: Drug Repurposing Opportunities in Cancer
	5.1 Introduction
	5.2 Drug Repurposing
	5.3 Drug Repurposing Barriers
	5.4 Computational Approaches in Drug Repurposing
	5.5 Drug Repurposing in Cancer
		5.5.1 Importance of Drug Repurposing in Cancer Treatment
		5.5.2 Repurposing Small-Molecule Non-Oncology Drugs
			5.5.2.1 Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
				5.5.2.1.1 Aspirin
				5.5.2.1.2 Diclofenac
				5.5.2.1.3 Ibuprofen
				5.5.2.1.4 Naproxen
			5.5.2.2 Statins
				5.5.2.2.1 Simvastatin
			5.5.2.3 Antidiabetic Drugs
				5.5.2.3.1 Metformin
				5.5.2.3.2 Phenformin
			5.5.2.4 Selective Estrogen Receptor Modulators (SERMs)
				5.5.2.4.1 Raloxifene
			5.5.2.5 Antidepressants
				5.5.2.5.1 Imipramine
				5.5.2.5.2 Trifluoperazine
				5.5.2.5.3 Fluoxetine
			5.5.2.6 Antipsychotic
				5.5.2.6.1 Chlorpromazine
			5.5.2.7 Anticonvulsant
				5.5.2.7.1 Valproic Acid
			5.5.2.8 Antiviral Drugs
				5.5.2.8.1 Ritonavir
				5.5.2.8.2 Nelfinavir
				5.5.2.8.3 Lopinavir
			5.5.2.9 Antibiotics
				5.5.2.9.1 Ciprofloxacin
				5.5.2.9.2 Nifuroxazide
				5.5.2.9.3 Moxifloxacin
			5.5.2.10 Antifungals
				5.5.2.10.1 Clotrimazole
				5.5.2.10.2 Itraconazole
			5.5.2.11 Antiepileptic Drug
				5.5.2.11.1 Flunarizine
				5.5.2.11.2 Prazosin
			5.5.2.12 Antimalarials
				5.5.2.12.1 Amodiaquine
				5.5.2.12.2 Chloroquine
			5.5.2.13 Anthelmintics
				5.5.2.13.1 Mebendazole
				5.5.2.13.2 Niclosamide
				5.5.2.13.3 Albendazole
			5.5.2.14 Antirheumatics
				5.5.2.14.1 Leflunomide
				5.5.2.14.2 Auranofin
			5.5.2.15 Antilipidemic
				5.5.2.15.1 Fenofibrate
			5.5.2.16 Alcohol Antagonist Drug
				5.5.2.16.1 Disulfiram
		5.5.3 Repurposing Phytochemicals
			5.5.3.1 Resveratrol
			5.5.3.2 Quercetin
			5.5.3.3 Epigallocatechin-3-Gallate
			5.5.3.4 Fisetin
			5.5.3.5 Berberine
			5.5.3.6 Sanguinarine
			5.5.3.7 Caffeic Acid Phenethyl Ester
			5.5.3.8 Capsaicin
			5.5.3.9 Eugenol
			5.5.3.10 Caffeic Acid
			5.5.3.11 Oxymatrine
	5.6 Repurposed Non-Oncology Drugs in Clinical Trials for the Treatment of Different Cancers
	5.7 Future Prospects
	5.8 Concluding Remarks
	References
Chapter 6: Repurposing of Flavonoids as Promising Phytochemicals for the Treatment of Lung Carcinoma
	6.1 Introduction
		6.1.1 Classifications of Flavonoids
	6.2 Reported Flavonoids Against Lung Cancer
		6.2.1 Anticarcinogenic Properties and Targets of Flavonoids
		6.2.2 Molecular Mechanism of Action of Flavonoids
			6.2.2.1 Carcinogenic Metabolic Activation Pathway Targeting by Flavonoids
			6.2.2.2 Antiproliferative Activity
			6.2.2.3 Cell Signaling
			6.2.2.4 Apoptotic Effect
			6.2.2.5 Differentiation
			6.2.2.6 Antiangiogenic Effect
			6.2.2.7 Multidrug Resistance
			6.2.2.8 Antioxidant Activity
	6.3 Flavonoids and Their Reported Biological Activities
	6.4 Combination of Strategies and Futuristic Approaches
	6.5 Conclusions
	References
Chapter 7: Targeted Therapies Used in the Treatment of Non-Small-Cell Lung Cancer: An Overview
	7.1 Introduction
		7.1.1 Classification of Lung Cancer
		7.1.2 Risk Factors in Lung Cancer
		7.1.3 Diagnosis of NSCLC and Its Various Stages
	7.2 Treatment for Non-Small-Cell Lung Cancer
		7.2.1 Surgery
		7.2.2 Radiotherapy
		7.2.3 Chemotherapeutic Drugs
			7.2.3.1 First-Line Treatment for NSCLC
				7.2.3.1.1 Cisplatin (1978)
				7.2.3.1.2 Paclitaxel (2012)
				7.2.3.1.3 Methotrexate (2014)
				7.2.3.1.4 Vinorelbine (1994)
				7.2.3.1.5 Gemcitabine (1996)
			7.2.3.2 Second-Line Treatment for NSCLC
				7.2.3.2.1 Docetaxel (1999)
		7.2.4 Targeted Therapy Used for Curing of NSCLC
			7.2.4.1 Drugs Targeting Angiogenesis
				7.2.4.1.1 Antiangiogenic Agents
					VEGF Blockers
						Bevacizumab (2006)
						Ramucirumab (2014)
					MMP Blockers
						Batimastat
						Marimastat
						Prinomastat
						BAY12-95666 (Tanomastat)
						ONO-4817
				7.2.4.1.2 Vascular Targeting Agent
			7.2.4.2 Drugs Targeting EGFR
				7.2.4.2.1 Anti-EGFR Monoclonal Antibodies
					Cetuximab
				7.2.4.2.2 EGFR Tyrosine Kinase Inhibitors (TKIs)
					Gefitinib (2003)
					Erlotinib (2004)
					Afatinib (2013)
					Dacomitinib (2018)
				7.2.4.2.3 Inhibitors Target Cells with T790M Mutation
					Osimertinib (2015)
				7.2.4.2.4 Inhibitors Used for Squamous Cells
					Necitumumab (2015)
				7.2.4.2.5 Others
					Rociletinib
					EGF816 (Nazartinib)
					ASP8273
					HM61713 (Olmutinib)
			7.2.4.3 Drugs Targeting ALK Receptor
				7.2.4.3.1 Crizotinib (2011)
				7.2.4.3.2 Ceritinib (2014)
				7.2.4.3.3 Alectinib (2015)
				7.2.4.3.4 Brigatinib (2017)
				7.2.4.3.5 Lorlatinib (2018)
			7.2.4.4 Drugs Targeting BRAF Receptor
				7.2.4.4.1 Dabrafenib (2013)
				7.2.4.4.2 Trametinib (2017)
				7.2.4.4.3 Vemurafenib (2011)
				7.2.4.4.4 Selumetinib (AZD6244)
			7.2.4.5 Drugs Targeting MET Receptor
				7.2.4.5.1 Cabozantinib
			7.2.4.6 Drug Targeting HER2
			7.2.4.7 Drugs Targeting ROS-1 Receptor
				7.2.4.7.1 Entrectinib (2019)
			7.2.4.8 Drugs Targeting RET Receptor
				7.2.4.8.1 Vandetanib
				7.2.4.8.2 Lenvatinib
				7.2.4.8.3 Ponatinib
			7.2.4.9 Drugs Targeting NTRK1 Receptor
			7.2.4.10 Drugs Targeting PIK3CA
				7.2.4.10.1 LY3023414
				7.2.4.10.2 PQR309 (Bimiralisib)
			7.2.4.11 Drugs Targeting MEK-1 Receptor
				7.2.4.11.1 Cobimetinib
	7.3 Conclusion
	References
Chapter 8: Drug Repurposing in Cancer
	8.1 Introduction
		8.1.1 Advantages
		8.1.2 Challenges
			8.1.2.1 Dosing and Safety
			8.1.2.2 Data Availability
			8.1.2.3 Intellectual Property
	8.2 Drug Repurposing in Cancer Therapy
		8.2.1 Cytostatic Agents for Cancer Therapy
			8.2.1.1 Aspirin
			8.2.1.2 Metformin
			8.2.1.3 Statins
	8.3 Target Prediction in Cancer
		8.3.1 Structure-Based Target Prediction
			8.3.1.1 Docking
			8.3.1.2 Binding Site Prediction
			8.3.1.3 Pharmacophore-Based Screening
			8.3.1.4 Interaction Similarity
		8.3.2 Cheminformatics-Based Target Prediction
	8.4 Effect of DR in Different Pathways
		8.4.1 Wnt Pathway
		8.4.2 mTOR Signaling Pathway-The Role of AMPK Activation in Aspirin-Mediated mTOR Inhibition
		8.4.3 Inhibition of Ras/ERK and Ras/mTOR Pathways
		8.4.4 ERK/Akt Pathway
		8.4.5 AMPK-NF-κB Signaling
	8.5 Large Data Analysis and Precise Personal Therapy
		8.5.1 Genome-Wide Association Studies (GWAS)
		8.5.2 Electronic Health Records (EHRs)
		8.5.3 PheWAS
	8.6 Conclusion
	References
Chapter 9: Targeting the Ubiquitin Machinery for Cancer Therapeutics
	9.1 Introduction
		9.1.1 Ubiquitin-Proteasome System
			9.1.1.1 Ubiquitin
			9.1.1.2 Proteasome Machinery
		9.1.2 Classification of Ubiquitination and Deubiquitination Enzymes
			9.1.2.1 E1-Activating Enzyme
			9.1.2.2 E2-Conjugating Enzyme
			9.1.2.3 E3 Ubiquitin Ligase
			9.1.2.4 Deubiquitination Enzymes (DUBs)
		9.1.3 Role of Ubiquitination in Tumorigenesis
			9.1.3.1 Tumor Metabolism
			9.1.3.2 Tumor Microenvironment Modulation
			9.1.3.3 Cancer Stem Cells (CSCs) Stemness Maintenance
		9.1.4 Deregulation of the Ubiquitin System and Cancer
			9.1.4.1 Dysregulation of E3 Ligases
			9.1.4.2 Dysregulation of Deubiquitinating Enzymes
		9.1.5 Targeting the Ubiquitin-Proteasome System
			9.1.5.1 Targeting the E1/E2 Enzyme
			9.1.5.2 Targeting the E3 Enzyme
			9.1.5.3 Targeting DUBs
			9.1.5.4 Targeting Proteasome Activity
	9.2 Conclusions and Future Perspectives
	References
Chapter 10: Repurposing of Serotonin Pathway Influencing Drugs for Potential Cancer Therapy and Antimicrobial Functions
	10.1 Introduction
	10.2 Role of Serotonin and Serotonin Receptors in the Immunomodulation
	10.3 Classes of Drugs Involved with the Serotonin Pathway
		10.3.1 Antidepressants
		10.3.2 Antiemetics
		10.3.3 Antipsychotics
	10.4 Probable Repurposing/Repositioning of Antidepressants and Antipsychotics for Cancer Therapy and Antimicrobial Treatment
	10.5 Conclusion
	References
Chapter 11: Drug Repurposing for Hematological Malignancies
	11.1 Introduction
	11.2 How Drug Repurposing Can Help in Oncotherapeutics?
		11.2.1 De Novo Drug Synthesis
			11.2.1.1 Drug Discovery
				11.2.1.1.1 Target Identification/Discovery
					Target-Centric Drug Discovery
					Phenotype-Centric Drug Discovery
						Direct Approach of Target Deconvolution
						Indirect Approach of Target Deconvolution
				11.2.1.1.2 Target Validation
				11.2.1.1.3 Lead Identification
				11.2.1.1.4 Lead Optimization
			11.2.1.2 Preclinical Development
				11.2.1.2.1 Investigational New Drug Application (IND) Filing
			11.2.1.3 Clinical Trials/Development
				11.2.1.3.1 Phase 0
				11.2.1.3.2 Phase 1: Safety
				11.2.1.3.3 Phase 2: Efficacy
				11.2.1.3.4 Phase 3
			11.2.1.4 FDA Drug Review and Approval
			11.2.1.5 Postmarket Drug Safety Monitoring (Phase 4)
	11.3 Drug Repurposing/Repositioning
	11.4 The Drug Repurposing Overview
	11.5 Profiles of Drug Repurposing
	11.6 Approaches of Drug Repurposing
		11.6.1 Experimental Approach
		11.6.2 Computational Approaches
			11.6.2.1 Drug-Centric Repositioning
			11.6.2.2 Target-Centric Repositioning
			11.6.2.3 Disease-Centric Repositioning
			11.6.2.4 Signature-Based Approaches
			11.6.2.5 Network-Based Approaches
			11.6.2.6 Mixed Approach
	11.7 Drug Repurposing for Hematological Malignancies
	11.8 Leukemia
		11.8.1 Acute Lymphoid Leukemia (ALL)
			11.8.1.1 Tigecycline (TGC)
			11.8.1.2 Tamoxifen (TAM)
			11.8.1.3 Cannabidiol (CBD)
		11.8.2 Chronic Lymphoid Leukemia (CLL)
			11.8.2.1 Simvastatin
			11.8.2.2 Auranofin
		11.8.3 Acute Myeloid Leukemia (AML)
			11.8.3.1 Valproic Acid
			11.8.3.2 Artesunate
		11.8.4 Chronic Myeloid Leukemia (CML)
			11.8.4.1 Celecoxib
			11.8.4.2 Pioglitazone
	11.9 Lymphoma
		11.9.1 Hodgkin´s Lymphoma (HL)
			11.9.1.1 Verapamil (VRP)
		11.9.2 Non-Hodgkin´s Lymphoma (NHL)
		11.9.3 Aggressive Diffuse Large B-Cell Lymphoma
			11.9.3.1 Auranofin
		11.9.4 Multiple Myeloma (MM)
			11.9.4.1 Thalidomide
			11.9.4.2 Nelfinavir
	11.10 Status of Drug Repurposing in Hematological Malignancies
	11.11 Intellectual Property and Regulatory Issues in Drug Repurposing
	11.12 Conclusion
	References
Chapter 12: Drug Repurposing for, ENT and Head and Neck, Infectious and Oncologic Diseases: Current Practices and Future Possi...
	12.1 Section A: Repurposing Novel Antimetabolic Imidazole Drug for Infectious Airways Diseases with Implications in Developmen...
		12.1.1 Introduction
		12.1.2 Novel Olfactory Druggable Targets for Clinical Management of COVID-19 and COVID-19-Associated Mucormycosis (CAM)
		12.1.3 Scope of Intranasal Sprays for Treating Infectious Airway Diseases
		12.1.4 Literature in Support of Implication of our Our Preliminary Findings for Developing Anti-IFI Intranasal Sprays
		12.1.5 Challenges in the COVID-19 and CAM Therapeutics
		12.1.6 Repurposing Natural Azoles in COVID-19-Associated Mucormycosis
			12.1.6.1 Mucorales and Antifungal Resistance
			12.1.6.2 L Carnosine/Anserine Azoles with Antidiabetic and Anti-COVID (Host Targeting) Potential for Repurposing in CAM
		12.1.7 Iron Metabolism and Homeostasis in Fungal Infections
			12.1.7.1 Mitochondrial-Driven Iron Metabolism in Azole Drug Resistance
		12.1.8 Novel Azoles Targeting Host-Fungal Interactions for Drug Repurposing in CAM
			12.1.8.1 Novelty of Repurposing L-Carnosine in Mucormycosis and CAM
	12.2 Section B: Current Use and Evidence in Otolaryngology and Head and Neck Surgery (ENT)
		12.2.1 Introduction
			12.2.1.1 Sinonasal and Airway Diseases
			12.2.1.2 Diseases of the EAR
			12.2.1.3 Diseases of Head and Neck
	References
Chapter 13: Repurposing of Immunomodulators for the Treatment of Cancer with QSAR Approaches
	13.1 Introduction
	13.2 Immunotherapy as Anticancer
	13.3 Prospects for Repurposing Drugs for Cancer Treatment
	13.4 Natural Derivatives as a Source of Immunomodulator
		13.4.1 Maslinic Acid
		13.4.2 Mushroom Species
		13.4.3 Curcumin
		13.4.4 Piperine
		13.4.5 Cardamom (Elettaria Cardamomum)
		13.4.6 Gingerol
		13.4.7 Adriamycin
		13.4.8 Imide Drugs
		13.4.9 Metformin
			13.4.9.1 QSAR Approaches
	References
Chapter 14: Reverse Translational Approach in Repurposing of Drugs for Anticancer Therapy
	14.1 Introduction
	14.2 Prospective of Reverse Translational Research Approach in Drug Development for Cancer Therapy
	14.3 Opportunities in Drug Repurposing Approach
	14.4 Strategies for Drug Repurposing
	14.5 Necessity of Drug Repurposing for Managing Cancer
	14.6 Reverse Translation for Drug Repurposing in Anticancer Therapies
	14.7 Antibiotics
		14.7.1 Clarithromycin
		14.7.2 Doxycycline
		14.7.3 Minocycline
		14.7.4 Tigecycline
		14.7.5 Nitroxoline
		14.7.6 Cephalosporins
		14.7.7 Fluoroquinolones
	14.8 Antivirals
		14.8.1 Ganciclovir
		14.8.2 Lopinavir
		14.8.3 Indinavir
		14.8.4 Cidofovir
		14.8.5 Efavirenz
		14.8.6 Maraviroc
		14.8.7 Nelfinavir
		14.8.8 Ritonavir
		14.8.9 Ribavirin
		14.8.10 Zidovudine
		14.8.11 Amantadine
	14.9 Antifungals
		14.9.1 Itraconazole
		14.9.2 Ketoconazole
		14.9.3 Clioquinol
		14.9.4 Clotrimazole
		14.9.5 Terbinafine
	14.10 Antimalarial Drugs
	14.11 Anthelmintic Agents
		14.11.1 Mebendazole, Niclosamide, Albendazole and Ivermectin
		14.11.2 Ivermectin
		14.11.3 Nitazoxanide
		14.11.4 Praziquantel
		14.11.5 Levamisole
	14.12 Expanding Opportunities of Drug Repurposing
		14.12.1 Treatment of COVID-19 Along with Cancer
		14.12.2 Precision Medicines Development
	14.13 Conclusion and Future Prospects
	References
Chapter 15: Therapeutic Targeting of Antineoplastic Drugs in Alzheimer´s Disease: Discovered in Repurposed Agents
	15.1 Introduction
	15.2 The Common Shared Link Between Cancer and AD
	15.3 Pathophysiological Pathways Shared Between Cancer and AD Cell Cycle
		15.3.1 MAPK Pathway
		15.3.2 Wnt Pathway
		15.3.3 Redox Signaling Pathway
		15.3.4 PI3K/AKT/mTOR Pathway
		15.3.5 Anticancer Agents Can Be Repurposed for AD
		15.3.6 Bexarotene
		15.3.7 Tamibarotene (Am80)
		15.3.8 Nilotinib
		15.3.9 Thalidomide
		15.3.10 Imatinib (Gleevec)
		15.3.11 Sunitinib
		15.3.12 Pazopanib
		15.3.13 Carmustine (BCNU)
		15.3.14 Paclitaxel (Taxol)
	15.4 Conclusion and Future Perspective
	References
Chapter 16: Repurposing of Drugs for the Treatment of Microbial Diseases
	16.1 Introduction
	16.2 Antimicrobial Agents: Mechanism of Resistance
	16.3 Need of Repurposing of Drugs for Microbial Diseases
	16.4 Repurposing of Drugs as Antimicrobial Agents
		16.4.1 Repurposing of Anticancer Drugs for Microbial Diseases
		16.4.2 Repurposing of Anti-inflammatory Drugs for Microbial Diseases
		16.4.3 Repurposing of Anthelmintic Drugs for Microbial Diseases
		16.4.4 Repurposing of Cardiovascular Drugs for Microbial Diseases
		16.4.5 Repurposing of Antipsychotic and Antidepressant Drugs for Microbial Diseases
		16.4.6 Repurposing of Antihistaminic Agents for Microbial Diseases
		16.4.7 Other Drugs Repurposed Against Microbial Infections
	16.5 Conclusion
	References
Chapter 17: Repurposing Anti-inflammatory Agents in the Potential Treatment of SARS-COV-2 Infection
	17.1 Introduction
	17.2 Epidemiology of COVID-19
	17.3 Inflammatory Reaction in Pathophysiology of COVID-19
	17.4 Pathways Involved in Inflammation
		17.4.1 JAK/STAT Pathway
		17.4.2 NF-κB Pathway
		17.4.3 Toll-like Receptor Pathway
		17.4.4 MAPK Pathway
		17.4.5 COX Pathway
		17.4.6 Inflammasome
	17.5 Inhibitors/Targeting Agents of Inflammatory Pathways of JAK-STAT, NF-κB, MAPK, COX, iNOS, etc.
		17.5.1 JAK-STAT Inhibitors/Targeting Agents
			17.5.1.1 Tofacitinib
			17.5.1.2 Baricitinib
			17.5.1.3 Ruxolitinib
			17.5.1.4 Other Jakinibs
		17.5.2 COX Inhibitors/Targeting Agents
		17.5.3 MAPK Inhibitors/Targeting Agents
		17.5.4 NF-κB Inhibitors/Targeting Agents
		17.5.5 iNOS Inhibitors/Targeting Agents
	17.6 Conclusion
	References
Chapter 18: Repurposing Drugs for Viruses and Cancer: A Novel Drug Repositioning Strategy for COVID-19
	18.1 Introduction
	18.2 Classic Examples of Anticancer Drug Repositioning
		18.2.1 Zidovudine
		18.2.2 Cardiac Glycosides
	18.3 Anticancer Drug Candidates for Previous SARS-CoV and MERS-CoV
		18.3.1 Imatinib
		18.3.2 Saracatinib
		18.3.3 Homoharringtonine
	18.4 The General Life Cycle and Pathogenesis
		18.4.1 Viral Entry and Membrane Fusion
		18.4.2 Replication and Virus Assembly
	18.5 Pathophysiology
	18.6 Anticancer Drugs with Potential Antiviral Properties
		18.6.1 Inhibition of Virus Replication by Targeting the Main Protease (M pro)
			18.6.1.1 Carmofur
			18.6.1.2 Carfilzomib
		18.6.2 Inhibition of Viral Protein Synthesis by Targeting Transcription-Complex Proteins
			18.6.2.1 Zotatifin
			18.6.2.2 Plitidepsin
		18.6.3 Inhibition of Viral Entry into Hostspiepr146 Cells
			18.6.3.1 Toremifene
	18.7 Targeting Cellular Pathway Mechanisms as a Strategy for Drug Repositioning
		18.7.1 PI3K/AKT/mTOR
		18.7.2 STAT-3
		18.7.3 VEGF
	18.8 Limitations and Future Perspectives of Drug Repositioning
		18.8.1 Accessibility to Data and Compound
		18.8.2 Drug Safety and Toxicity
		18.8.3 Exhaustion of Conventional Drug Repositioning Strategies
		18.8.4 Intellectual Property Protection
		18.8.5 Challenges of Bioinformatics Approaches
	18.9 Conclusion
	References
Chapter 19: Drug Repurposing for COVID-19 Therapy: Pipeline, Current Status and Challenges
	19.1 Introduction
	19.2 Advantages of Drug Repurposing
	19.3 Drug Repurposing for COVID-19 Treatment
	19.4 Drug Repurposing Pipeline for COVID-19 Therapy
		19.4.1 Wet Lab-Based Research
		19.4.2 Dry Lab-Based Research
			19.4.2.1 Systems Biology
			19.4.2.2 Computational Structural Biology
			19.4.2.3 Mathematical Biology
			19.4.2.4 Serendipitous Discovery
			19.4.2.5 Screening of Repurposed Drugs
	19.5 Current Status of Drug Repurposing for COVID-19 Therapy
		19.5.1 Drugs That Show Antiviral Activity by Targeting Viral Proteins
		19.5.2 Drugs That Show Antiviral Activity by Targeting the Host
		19.5.3 Drugs That Act Indirectly by Reducing the Disease Severity
	19.6 Challenges in Drug Repurposing Against COVID-19
		19.6.1 Sub-optimal In Vivo Activity of the Drug Compounds
		19.6.2 Limited Access to Compounds and Related Data
	19.7 Conclusion and Future Prospects
	References
Chapter 20: 2-Deoxy-d-Glucose: A Repurposed Drug for COVID-19 Treatment
	20.1 Introduction
	20.2 Drug-Target Interaction Profiles Are a Natural Extension of Molecular Docking
	20.3 Comparison of COVID-19 Progression with Cancer
	20.4 2-DG Molecule as a Glucose Analog
	20.5 Pharmacological Properties of 2-DG of Relevance to Cancer and COVID-19 Therapies
		20.5.1 Glycolysis Inhibition
		20.5.2 Autophagy Induction
		20.5.3 Apoptosis Induction
		20.5.4 Protein N-Glycosylation
	20.6 2-DG as an Adjuvant to Cancer Therapy
	20.7 2-DG Against Various Viral Diseases
	20.8 Rationale for Using 2-DG as an Anti-COVID Drug
	20.9 Use of 2-DG Against SARS-CoV-2
	20.10 Possible Mechanism of Action of Use of 2-DG Against SARS-CoV-2
	20.11 Future Perspective
	20.12 Conclusion
	References
Chapter 21: Repurposing Methylene Blue for the Management of COVID-19: Prospects, Paradox, and Perspective
	21.1 Introduction
	21.2 Problems with Conventional Therapy
	21.3 Rationale and Hypothesis of Methylene Blue as an Adjunct to Standard of Care
	21.4 Value Addition by Photoirradiation
	21.5 Utility of MB in Fungal Superinfections Associated With COVID-19
	21.6 Risk-Benefit Analysis
	21.7 Prospects, Paradox, and Perspective for COVID-19 and the Associated Complications
	21.8 Conclusion
	References
Chapter 22: Drug Repurposing in COVID-19 and Cancer: How Far Have We Come?
	22.1 Introduction
	22.2 Success Stories of Drug Repurposing
	22.3 Drug Repurposing and Infectious Diseases
		22.3.1 COVID-19
		22.3.2 Cancer
	22.4 Challenges and Future Perspectives
	References
Chapter 23: Repurposing of Doxycycline to Attenuate Influenza Virus Pathogenesis Via Inhibition of Matrix Metalloproteinases i...
	23.1 Neutrophils and Influenza Virus-Induced Lung Injury
	23.2 Functions of Matrix Metalloproteinases
	23.3 Repurposing Doxycycline to Mitigate Influenza-Induced Tissue Injury
	23.4 Study Objectives
	23.5 Materials and Methods
	23.6 Results and Discussion
		23.6.1 Mouse-Adapted Influenza H3N2 P16 Virus Infection of MPRO Neutrophils Enhances MMP-2 and MMP-9 Protein Expression, Gelat...
		23.6.2 Doxycycline Treatment Inhibits MMP-2 and MMP-9 Protein Expression, Gelatinase Activity, and MMP-9 Gene Expression in Ne...
		23.6.3 Future Perspectives and Repurposing Doxycycline for Other Infections
	23.7 Summary
	References
Chapter 24: Therapeutic Repurposing Approach: New Opportunity for Developing Drugs Against COVID-19
	24.1 Introduction
	24.2 COVID-19 Risk Factors
	24.3 Pathophysiology Targets for COVID
	24.4 Clinical Feature
		24.4.1 Asymptomatic Phase (Stage 1)
		24.4.2 Stage 2: Upper Airway and Airway Response (in the Coming Days)
		24.4.3 Stage 3: Hypoxia, Ground-Glass Infiltration, and Progression to ARDS
	24.5 Therapeutic Approach for COVID-19
	24.6 Repurposing of the Drugs to Cure COVID-19
		24.6.1 Repurposed Drugs That Act on Virus-Related Targets
		24.6.2 Repurposed Drugs Act Through Inhibition of Viral Enzymes
		24.6.3 Repurposed Drugs Targeting the Virus Uptake Pathways
		24.6.4 Repurposed Drugs Act Through Host Targets Such as Antiviral Immunity
		24.6.5 Other Repurposed Drugs for the Treatment of COVID
	24.7 Conclusion and Future Perspective
	References
Chapter 25: Repurposing of Therapeutic Approaches for the Treatment of Vitiligo
	25.1 Introduction
	25.2 Medical Treatment of Vitiligo
	25.3 Drug Repositioning
	25.4 Repurposing of Approved Therapeutics for Vitiligo
		25.4.1 Treatment Goals
		25.4.2 Disadvantage of Current Vitiligo Therapeutics
		25.4.3 Advantage Associated with Repurposing of Drugs
		25.4.4 Mechanism Target-Vitiligo
	25.5 Available Therapy
		25.5.1 Topical Corticosteroids
		25.5.2 Topical Calcineurin Inhibitors
		25.5.3 Topical Vitamin D Analogues
		25.5.4 Topical Prostaglandin Analogues
		25.5.5 Topical Antioxidants
		25.5.6 Phototherapy
		25.5.7 PUVA-Psoralen Plus UVA-A
		25.5.8 Narrow Band UVB
		25.5.9 Other Photochemotherapies
		25.5.10 Lasers
			25.5.10.1 Monochromatic Excimer Laser (MEL)
			25.5.10.2 Helium Neonspiepr146 Laser
	25.6 Systemic Treatment
	25.7 Surgical Methods
		25.7.1 Cellular Grafts
	25.8 Emerging Treatments by Drug Repurposing
		25.8.1 Minocycline
		25.8.2 Methotrexate
		25.8.3 Cyclosporine
		25.8.4 JAK-STAT Inhibitors
		25.8.5 Ruxolitinib
		25.8.6 STAT Inhibitors
		25.8.7 Alpha-Melanocyte-Stimulating Hormone (MSH)
		25.8.8 UVA1 Lasers
		25.8.9 Photodymanic Therapy
		25.8.10 Oral Antioxidants
		25.8.11 Topical Immunosuppressants
		25.8.12 Basic Fibroblast Growth Factor
	25.9 Targeted Immunotherapy
	25.10 Future Scope
	25.11 Reported Clinical Trials
	25.12 Future Prospects and Conclusion
	References
Chapter 26: Emerging Infections and Their Management
	26.1 Emerging Infections
	26.2 Origin of Emerging Infections
	26.3 ESKAPE Pathogen
	26.4 Variations in the Pathogenesis of EIDs
	26.5 Identification
		26.5.1 Markers
		26.5.2 Databases
		26.5.3 Hotspots
	26.6 Management of EIDs
		26.6.1 Surveillance
		26.6.2 Risk Assessment
		26.6.3 Repurposing of Drugs
	References
Chapter 27: Repurposing of Minocycline, a Tetracycline Antibiotic, for Neurodegenerative Disorders
	27.1 Introduction
	27.2 Minocycline, a Tetracycline Antibiotic
		27.2.1 Structure
		27.2.2 Physicochemical Properties
		27.2.3 ADME profile
			27.2.3.1 Absorption
			27.2.3.2 Distribution
			27.2.3.3 Metabolism
			27.2.3.4 Excretion
			27.2.3.5 Half-Life and Clearance
			27.2.3.6 Adverse Effects and Toxicity
		27.2.4 Mechanism of Action
			27.2.4.1 Anti-microbial Action
				27.2.4.1.1 Translation
			27.2.4.2 Anti-apoptotic Actions
			27.2.4.3 Anti-inflammatory Action
			27.2.4.4 Inhibition of Matrix Metalloproteinases
			27.2.4.5 Effect of Minocycline on Protein Misfolding
		27.2.5 Why Can Minocycline Be Repurposed in Neurodegenerative Diseases?
	27.3 Repurposing of Minocycline in Neurodegenerative Diseases (Pre-clinical & Clinical Evidence)
		27.3.1 Alzheimer´s & Other Related Dementias
			27.3.1.1 Pathology
			27.3.1.2 Pre-clinical Trails
			27.3.1.3 Clinical Trials
		27.3.2 Parkinson´s Disease
			27.3.2.1 Pre-clinical Studies
			27.3.2.2 Clinical Trails
		27.3.3 Huntington's Disease
			27.3.3.1 Pre-clinical Evidence
			27.3.3.2 Clinical Evidence
		27.3.4 Amyotrophic Lateral Sclerosis (ALS)
			27.3.4.1 Pathophysiology
				27.3.4.1.1 Causes
				27.3.4.1.2 Treatment
				27.3.4.1.3 Minocycline in ALS
				27.3.4.1.4 Minocycline and Riluzule (Rilitek)
		27.3.5 Multiple Sclerosis
			27.3.5.1 Diagnosis
			27.3.5.2 Minocycline in Multiple Sclerosis
			27.3.5.3 Mechanism of Action
			27.3.5.4 Pilot Study of Minocycline in RRMS
			27.3.5.5 Minocycline and Interferon-β
	27.4 Future Perspectives
	27.5 Conclusion
	References