Rashid Ali, PhD, is an assistant professor in the Department of Chemistry, Jamia Millia Islamia, New Delhi, India after receiving his PhD from the Indian Institute of Technology Bombay in organic and supramolecular chemistry. He has more than 50 research articles in international journals as well as multiple book chapters. Shahid-ul-Islam, PhD, is a Research Scientist at the Department of Textile & Fiber Engineering, Indian Institute of Technology Delhi (IIT). His areas of interest are antimicrobial coatings, green chemistry, fibers & polymers, polymeric composites and nanocomoposites, and nano-biotechnology. He has published numerous peer-reviewed research articles in journals of high repute as well as contributions to several books published by the Wiley-Scrivener imprint.

• Preface xi1 Introduction to Ivermectin 1Aeyaz Ahmad Bhat, Atif Khurshid Wani, Tahir ul Gani Mir and Nahid Akther1.1 Introduction 11.2 Sources and Synthesis 31.3 Pharmacological Potential of Ivermectin 41.4 Ivermectin's Beneficial Role in Cattle 81.5 Ivermectin in the Treatment of COVID-19 81.6 Toxicity of Ivermectin 101.7 Conclusion 132 Historical Background of and Synthetic Approaches to Ivermectin (IVM) and its Homologues 23Shakeel Alvi, Mohd Kamil Hussain and Rashid Ali2.1 Introduction 242.2 Synthetic Approaches Towards the Construction of IVM and Analogues 292.3 Biosynthesis 292.4 Chemical Synthetic Pathway 332.5 Crystal Structure 422.6 Conclusion and Outlook 423 Ivermectin as a Repurposed Drug for COVID-19 47Hari Madhav, Mohammad Rehan, Nasimul Hoda and Ehtesham Jameel3.1 Introduction 473.2 Symptoms of COVID-19 503.3 Repurposing of the Drugs 523.4 Repurposed Drugs for COVID-19 523.5 Repurposing of Ivermectin for COVID-19 533.6 Proposed Possible Mechanism of Action 543.7 SARS COVID-19 Clinical Studies with Ivermectin 553.8 Conclusions 593.9 Acknowledgments 604 Ivermectin as an Anti-Parasitic Agent 69Areeba Rahman, Abdulaziz S. Alouffi, Mohammad Husain and Abdur Rub4.1 Introduction 704.2 Use of Ivermectin Against Various Human Parasitic Infections 764.3 Mode of Action Against Various Parasites 834.4 Conclusions 834.5 Acknowledgements 845 Emerging Paradigm of Ivermectin and its Hybrids in Elimination of Malaria 93Iram Irfan, Diksha Shahi, Mukesh C. Joshi, Shailja Singh and Mohammad Abid5.1 Introduction 945.2 Malaria 955.3 Life Cycle of Malaria 1005.4 Drug Against Hepatic Malarial Stage 1055.5 About Ivermectin 1065.6 Designing and Synthesis of Ivermectin Inhibitors 1075.7 Conclusions 1125.8 Acknowledgments 1136 Ivermectin: A Potential Repurposed Anti-Cancer Therapeutic 121Mohd Kamil Hussain, Rashid Ali, Shakir Ahamad, Mohammad Faheem Khan and Mohammad Saquib6.1 Introduction 1226.2 Mechanism of Anti-Carcinogenesis 1246.3 Activation of Chloride Ion Channels 1256.4 Anti-Mitotic Effect and Inhibition of Angiogenesis 1276.5 Inhibition of Mitochondrial Respiration 1276.6 Inhibitor of Cancer Stem Cells (CSCs) 1286.7 Induction of Immunogenic Cell Death (ICD) 1286.8 Epigenetic Modulator 1296.9 Induction PAK1-Mediated Cytostatic Autophagy 1296.10 Inhibition of P-glycoprotein (P-gp) 1306.11 Inhibition of Yes-Associated Protein 1 (YAP1) 1306.12 Inhibition of RNA Helicase 1316.13 Caspase-Dependent Apoptosis 1326.14 Activation of Transcription Factor E3 (TFE3) 1326.15 Inhibition of Wnt-TCF Pathway Responses 1326.16 Conclusions 1337 Ivermectin as an Anti-Inflammatory Agent 141Mudasir Nabi Peerzada and Saurabh Verma7.1 Introduction 1417.2 Ant-Inflammatory Action of Ivermectin 1477.3 Conclusions 1558 Ivermectin: An Anthelminthic and Insecticide 163Manisha Arora Pandit and Tarkeshwar8.1 Introduction 1648.2 Ivermectin as an Anthelmintic 1658.3 Insecticidal Activity of Ivermectin 1769 Potential Applications of Ivermectin (IVM) in Dermatology 199Vikrant Jayant and Rashid Ali9.1 Introduction 2009.2 Mechanism of Action, Toxicity, and Side Effects of IVM 2039.3 Motivational Approach of IVM in the Treatment of Skin 2069.4 Role of IVM with Good Anti-Parasitic Properties Against the Infection of Skin 2129.5 Importance of IVM as an Anti-Cancer or Anti-Tumor Agent in Curing the Skin 2199.6 Social Value of IVM in the Medical Care of Red Scrotum Syndrome (RSS) 2209.7 Utility of IVM as an Anti-Inflammatory Drug in the Treatment of Skin-Related Issues 2219.8 Conclusions 22410 Antiviral Uses of Ivermectin 231Shabnam Kawoosa, Rabiah Bashir, Sheeba Nazir, Zubaid-ul-Khazir Rather, Gulam Nabi Yatoo and Nisar Ahmad Khan10.1 Introduction 23110.2 Mechanism of Action of Ivermectin 23310.3 Anti-Viral Effects Against Various DNA and RNA Viruses 23610.4 Conclusion 24211 Toxicology, Safety, and Environmental Aspects of Ivermectin 247Ayesha Akhtar, Nasreen A. Mazumdar and Afreen Inam11.1 Introduction 24711.2 Ivermectin’s Antiparasitic Activity 24911.3 Pharmacology 25011.4 Adverse Effects in Humans and Animals 25111.5 Ivermectin and Ectoparasites 25511.6 Environmental Impact and Biodegradation of Ivermectin 25811.7 Conclusion 259References 259Index 265

Rashid Ali, PhD, is an assistant professor in the Department of Chemistry, Jamia Millia Islamia, New Delhi, India after receiving his PhD from the Indian Institute of Technology Bombay in organic and supramolecular chemistry. He has more than 50 research articles in international journals as well as multiple book chapters. Shahid-ul-Islam, PhD, is a Research Scientist at the Department of Textile & Fiber Engineering, Indian Institute of Technology Delhi (IIT). His areas of interest are antimicrobial coatings, green chemistry, fibers & polymers, polymeric composites and nanocomoposites, and nano-biotechnology. He has published numerous peer-reviewed research articles in journals of high repute as well as contributions to several books published by the Wiley-Scrivener imprint.

• Preface xi1 Introduction to Ivermectin 1Aeyaz Ahmad Bhat, Atif Khurshid Wani, Tahir ul Gani Mir and Nahid Akther1.1 Introduction 11.2 Sources and Synthesis 31.3 Pharmacological Potential of Ivermectin 41.4 Ivermectin's Beneficial Role in Cattle 81.5 Ivermectin in the Treatment of COVID-19 81.6 Toxicity of Ivermectin 101.7 Conclusion 132 Historical Background of and Synthetic Approaches to Ivermectin (IVM) and its Homologues 23Shakeel Alvi, Mohd Kamil Hussain and Rashid Ali2.1 Introduction 242.2 Synthetic Approaches Towards the Construction of IVM and Analogues 292.3 Biosynthesis 292.4 Chemical Synthetic Pathway 332.5 Crystal Structure 422.6 Conclusion and Outlook 423 Ivermectin as a Repurposed Drug for COVID-19 47Hari Madhav, Mohammad Rehan, Nasimul Hoda and Ehtesham Jameel3.1 Introduction 473.2 Symptoms of COVID-19 503.3 Repurposing of the Drugs 523.4 Repurposed Drugs for COVID-19 523.5 Repurposing of Ivermectin for COVID-19 533.6 Proposed Possible Mechanism of Action 543.7 SARS COVID-19 Clinical Studies with Ivermectin 553.8 Conclusions 593.9 Acknowledgments 604 Ivermectin as an Anti-Parasitic Agent 69Areeba Rahman, Abdulaziz S. Alouffi, Mohammad Husain and Abdur Rub4.1 Introduction 704.2 Use of Ivermectin Against Various Human Parasitic Infections 764.3 Mode of Action Against Various Parasites 834.4 Conclusions 834.5 Acknowledgements 845 Emerging Paradigm of Ivermectin and its Hybrids in Elimination of Malaria 93Iram Irfan, Diksha Shahi, Mukesh C. Joshi, Shailja Singh and Mohammad Abid5.1 Introduction 945.2 Malaria 955.3 Life Cycle of Malaria 1005.4 Drug Against Hepatic Malarial Stage 1055.5 About Ivermectin 1065.6 Designing and Synthesis of Ivermectin Inhibitors 1075.7 Conclusions 1125.8 Acknowledgments 1136 Ivermectin: A Potential Repurposed Anti-Cancer Therapeutic 121Mohd Kamil Hussain, Rashid Ali, Shakir Ahamad, Mohammad Faheem Khan and Mohammad Saquib6.1 Introduction 1226.2 Mechanism of Anti-Carcinogenesis 1246.3 Activation of Chloride Ion Channels 1256.4 Anti-Mitotic Effect and Inhibition of Angiogenesis 1276.5 Inhibition of Mitochondrial Respiration 1276.6 Inhibitor of Cancer Stem Cells (CSCs) 1286.7 Induction of Immunogenic Cell Death (ICD) 1286.8 Epigenetic Modulator 1296.9 Induction PAK1-Mediated Cytostatic Autophagy 1296.10 Inhibition of P-glycoprotein (P-gp) 1306.11 Inhibition of Yes-Associated Protein 1 (YAP1) 1306.12 Inhibition of RNA Helicase 1316.13 Caspase-Dependent Apoptosis 1326.14 Activation of Transcription Factor E3 (TFE3) 1326.15 Inhibition of Wnt-TCF Pathway Responses 1326.16 Conclusions 1337 Ivermectin as an Anti-Inflammatory Agent 141Mudasir Nabi Peerzada and Saurabh Verma7.1 Introduction 1417.2 Ant-Inflammatory Action of Ivermectin 1477.3 Conclusions 1558 Ivermectin: An Anthelminthic and Insecticide 163Manisha Arora Pandit and Tarkeshwar8.1 Introduction 1648.2 Ivermectin as an Anthelmintic 1658.3 Insecticidal Activity of Ivermectin 1769 Potential Applications of Ivermectin (IVM) in Dermatology 199Vikrant Jayant and Rashid Ali9.1 Introduction 2009.2 Mechanism of Action, Toxicity, and Side Effects of IVM 2039.3 Motivational Approach of IVM in the Treatment of Skin 2069.4 Role of IVM with Good Anti-Parasitic Properties Against the Infection of Skin 2129.5 Importance of IVM as an Anti-Cancer or Anti-Tumor Agent in Curing the Skin 2199.6 Social Value of IVM in the Medical Care of Red Scrotum Syndrome (RSS) 2209.7 Utility of IVM as an Anti-Inflammatory Drug in the Treatment of Skin-Related Issues 2219.8 Conclusions 22410 Antiviral Uses of Ivermectin 231Shabnam Kawoosa, Rabiah Bashir, Sheeba Nazir, Zubaid-ul-Khazir Rather, Gulam Nabi Yatoo and Nisar Ahmad Khan10.1 Introduction 23110.2 Mechanism of Action of Ivermectin 23310.3 Anti-Viral Effects Against Various DNA and RNA Viruses 23610.4 Conclusion 24211 Toxicology, Safety, and Environmental Aspects of Ivermectin 247Ayesha Akhtar, Nasreen A. Mazumdar and Afreen Inam11.1 Introduction 24711.2 Ivermectin’s Antiparasitic Activity 24911.3 Pharmacology 25011.4 Adverse Effects in Humans and Animals 25111.5 Ivermectin and Ectoparasites 25511.6 Environmental Impact and Biodegradation of Ivermectin 25811.7 Conclusion 259References 259Index 265

Rashid Ali, PhD, is an assistant professor in the Department of Chemistry, Jamia Millia Islamia, New Delhi, India after receiving his PhD from the Indian Institute of Technology Bombay in organic and supramolecular chemistry. He has more than 50 research articles in international journals as well as multiple book chapters. Shahid-ul-Islam, PhD, is a Research Scientist at the Department of Textile & Fiber Engineering, Indian Institute of Technology Delhi (IIT). His areas of interest are antimicrobial coatings, green chemistry, fibers & polymers, polymeric composites and nanocomoposites, and nano-biotechnology. He has published numerous peer-reviewed research articles in journals of high repute as well as contributions to several books published by the Wiley-Scrivener imprint.

• Preface xi1 Introduction to Ivermectin 1Aeyaz Ahmad Bhat, Atif Khurshid Wani, Tahir ul Gani Mir and Nahid Akther1.1 Introduction 11.2 Sources and Synthesis 31.3 Pharmacological Potential of Ivermectin 41.4 Ivermectin's Beneficial Role in Cattle 81.5 Ivermectin in the Treatment of COVID-19 81.6 Toxicity of Ivermectin 101.7 Conclusion 132 Historical Background of and Synthetic Approaches to Ivermectin (IVM) and its Homologues 23Shakeel Alvi, Mohd Kamil Hussain and Rashid Ali2.1 Introduction 242.2 Synthetic Approaches Towards the Construction of IVM and Analogues 292.3 Biosynthesis 292.4 Chemical Synthetic Pathway 332.5 Crystal Structure 422.6 Conclusion and Outlook 423 Ivermectin as a Repurposed Drug for COVID-19 47Hari Madhav, Mohammad Rehan, Nasimul Hoda and Ehtesham Jameel3.1 Introduction 473.2 Symptoms of COVID-19 503.3 Repurposing of the Drugs 523.4 Repurposed Drugs for COVID-19 523.5 Repurposing of Ivermectin for COVID-19 533.6 Proposed Possible Mechanism of Action 543.7 SARS COVID-19 Clinical Studies with Ivermectin 553.8 Conclusions 593.9 Acknowledgments 604 Ivermectin as an Anti-Parasitic Agent 69Areeba Rahman, Abdulaziz S. Alouffi, Mohammad Husain and Abdur Rub4.1 Introduction 704.2 Use of Ivermectin Against Various Human Parasitic Infections 764.3 Mode of Action Against Various Parasites 834.4 Conclusions 834.5 Acknowledgements 845 Emerging Paradigm of Ivermectin and its Hybrids in Elimination of Malaria 93Iram Irfan, Diksha Shahi, Mukesh C. Joshi, Shailja Singh and Mohammad Abid5.1 Introduction 945.2 Malaria 955.3 Life Cycle of Malaria 1005.4 Drug Against Hepatic Malarial Stage 1055.5 About Ivermectin 1065.6 Designing and Synthesis of Ivermectin Inhibitors 1075.7 Conclusions 1125.8 Acknowledgments 1136 Ivermectin: A Potential Repurposed Anti-Cancer Therapeutic 121Mohd Kamil Hussain, Rashid Ali, Shakir Ahamad, Mohammad Faheem Khan and Mohammad Saquib6.1 Introduction 1226.2 Mechanism of Anti-Carcinogenesis 1246.3 Activation of Chloride Ion Channels 1256.4 Anti-Mitotic Effect and Inhibition of Angiogenesis 1276.5 Inhibition of Mitochondrial Respiration 1276.6 Inhibitor of Cancer Stem Cells (CSCs) 1286.7 Induction of Immunogenic Cell Death (ICD) 1286.8 Epigenetic Modulator 1296.9 Induction PAK1-Mediated Cytostatic Autophagy 1296.10 Inhibition of P-glycoprotein (P-gp) 1306.11 Inhibition of Yes-Associated Protein 1 (YAP1) 1306.12 Inhibition of RNA Helicase 1316.13 Caspase-Dependent Apoptosis 1326.14 Activation of Transcription Factor E3 (TFE3) 1326.15 Inhibition of Wnt-TCF Pathway Responses 1326.16 Conclusions 1337 Ivermectin as an Anti-Inflammatory Agent 141Mudasir Nabi Peerzada and Saurabh Verma7.1 Introduction 1417.2 Ant-Inflammatory Action of Ivermectin 1477.3 Conclusions 1558 Ivermectin: An Anthelminthic and Insecticide 163Manisha Arora Pandit and Tarkeshwar8.1 Introduction 1648.2 Ivermectin as an Anthelmintic 1658.3 Insecticidal Activity of Ivermectin 1769 Potential Applications of Ivermectin (IVM) in Dermatology 199Vikrant Jayant and Rashid Ali9.1 Introduction 2009.2 Mechanism of Action, Toxicity, and Side Effects of IVM 2039.3 Motivational Approach of IVM in the Treatment of Skin 2069.4 Role of IVM with Good Anti-Parasitic Properties Against the Infection of Skin 2129.5 Importance of IVM as an Anti-Cancer or Anti-Tumor Agent in Curing the Skin 2199.6 Social Value of IVM in the Medical Care of Red Scrotum Syndrome (RSS) 2209.7 Utility of IVM as an Anti-Inflammatory Drug in the Treatment of Skin-Related Issues 2219.8 Conclusions 22410 Antiviral Uses of Ivermectin 231Shabnam Kawoosa, Rabiah Bashir, Sheeba Nazir, Zubaid-ul-Khazir Rather, Gulam Nabi Yatoo and Nisar Ahmad Khan10.1 Introduction 23110.2 Mechanism of Action of Ivermectin 23310.3 Anti-Viral Effects Against Various DNA and RNA Viruses 23610.4 Conclusion 24211 Toxicology, Safety, and Environmental Aspects of Ivermectin 247Ayesha Akhtar, Nasreen A. Mazumdar and Afreen Inam11.1 Introduction 24711.2 Ivermectin’s Antiparasitic Activity 24911.3 Pharmacology 25011.4 Adverse Effects in Humans and Animals 25111.5 Ivermectin and Ectoparasites 25511.6 Environmental Impact and Biodegradation of Ivermectin 25811.7 Conclusion 259References 259Index 265