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