Viral Infections and Antiviral Therapies

Viral Infections and Antiviral Therapies provides comprehensive coverage of viral infections and their transmission. Coverage includes antiviral agents, therapeutics, their mechanisms and treatment strategies. The book is organized into four sections, including an introduction to antiviral therapies, viral infections and their transmission, antiviral agents and therapeutics, and a market overview and future developments. The chapters in each section of the book discuss various key topics that are contributed to by an international group of leading experts.

• Covers emerging and sexually transmitted viruses, including mode of transmission and pathophysiology of viral infections
• Describes antiviral agents and therapeutics for viruses such as rotaviruses, enteroviruses and coronaviruses
• Discusses strategies for the delivery of antiviral agents and vaccinations

• Language: English
• Publisher: Academic Press
• Release date: Nov 10, 2022
• ISBN: 9780323972420

Book preview

Front Cover for Viral Infections and Antiviral Therapies - 1st edition - by Amal Kumar Dhara, Amit Kumar Nayak

Viral Infections and Antiviral Therapies

Edited by

Amal Kumar Dhara

Department of Pharmacy, Contai Polytechnic, Purba Medinipur, West Bengal, India

Amit Kumar Nayak

Department of Pharmaceutics, Seemanta Institute of Pharmaceutical Sciences, Jharpokharia, Odisha, India

Table of Contents

Cover image

Title page

Copyright

List of contributors

Preface

Section I: Introduction

Chapter 1. Introduction to antiviral therapy

Abstract

1.1 Introduction

1.2 Virus replication cycle

1.3 Virus transmission and types of viral infections

1.4 Antiviral agents

1.5 Antiviral agents obtained from plant sources

1.6 Antiviral vaccines

1.7 Immunotherapy and role of nutraceuticals in viral infection

1.8 Challenges in the development of antiviral agents

1.9 Conclusion

References

Further reading

Section II: Viral infections and transmission

Chapter 2. Emerging viral diseases

Abstract

2.1 The everchanging landscape of infectious diseases

2.2 Causes of emergence

2.3 Ebola virus

2.4 Dengue virus

2.5 Chikungunya virus

2.6 West Nile virus

2.7 Zika virus

2.8 Yellow fever virus

2.9 Nipah virus

2.10 Influenza virus

2.11 Corona viruses

2.12 Prevention and control

2.13 The global response

2.14 Conclusions and the way forward

References

Chapter 3. Evolution and transmission of viruses

Abstract

3.1 Introduction

3.2 Viral Evolution

3.3 Transmission

3.4 Modes of transmission of viruses

3.5 Conclusion

References

Further reading

Chapter 4. Mode of viral infections and transmissions

Abstract

4.1 Introduction

4.2 Epidemiological triad and viral infection

4.3 Transmission of infection and clinical presentation

4.4 Modes of transmission of viral infection

4.5 Conclusion

4.6 Conflict of interest

References

Chapter 5. Transmission and intervention dynamics of SARS-CoV-2

Abstract

5.1 Introduction

5.2 Coronaviruses

5.3 Transmission characteristics of SARS-CoV-2

5.4 Intervention, strategies, and impacts

5.5 Summary

References

Chapter 6. Sexually transmitted viral infections

Abstract

6.1 Introduction

6.2 Human papilloma virus (HPV infection)

6.3 Effects of human papilloma virus on pregnancy and the neonate ,

6.4 Herpes simplex virus type 1 and 2

6.5 Human T-cell lymphotropic virus infection

6.6 Hepatitis A (HAV infection)

6.7 Hepatitis B (HBV infection)

6.8 Hepatitis C (HCV infection)

6.9 Prevention of sexually transmitted viral infections

6.10 Health education

6.11 Conclusion

References

Chapter 7. Testing viral infections

Abstract

7.1 Introduction

7.2 The purpose of laboratory diagnosis of viral infections

7.3 Sample collection, packaging, and transport

7.4 Type of specimen

7.5 Labeling/requisition form has the following information

7.6 Methods in diagnostic virology

7.7 Conclusion

Further reading

Chapter 8. Electron microscopic methods for virus diagnosis

Abstract

Abbreviations

8.1 Introduction

8.2 Other plant viruses

8.3 Concluding remarks and future trends

References

Section III: Antiviral agents and therapeutics

Chapter 9. Virotherapy

Abstract

9.1 Introduction

9.2 Oncolytic virus in common cancers and molecular changes observed during infection

9.3 Breast cancer

9.4 Lung cancer

9.5 Bladder and endometrial cancer

9.6 Renal and prostate cancer

9.7 Leukemia

9.8 Hepatocellular carcinoma

9.9 Melanoma

9.10 Brain cancer

9.11 Oncolytic viruses under clinical trial

9.12 Future directions

Softwares used for images

Author contribution

Conflicts of interest

Funding statement

Authors statement

References

Chapter 10. Challenges in designing antiviral agents

Abstract

10.1 Introduction

10.2 Strategies for the design of antiviral agents

10.3 Biggest challenging viruses

10.4 New trends, challenges, and opportunities

10.5 Conclusions

Acknowledgments

Conflict of interest

Consent for publication

References

Chapter 11. Anti-influenza agents

Abstract

11.1 Introduction

11.2 The virus

11.3 Anti-influenza agents

11.4 Conclusion

Acknowledgments

References

Chapter 12. Anti-herpes virus agents

Abstract

12.1 Herpes simplex: a DNA virus

12.2 Clinical administration of viral infection

12.3 Disadvantages of acyclovir

12.4 Ethnomedicine: a gift of God to solve the problems of synthetic drugs

12.5 Mode of action of plant-derived anti-herpes virus agents

12.6 Inhibition of virus replication

12.7 Inhibition of herpes simplex viruses by immunomodulation

12.8 Interference with virus release

12.9 Inhibition of herpes simplex viruses by autophagy

12.10 Inhibition of viral entry into the host cell

12.11 Conclusion

References

Chapter 13. Antiretroviral therapy

Abstract

13.1 Introduction

13.2 Formulation of antiretroviral treatment

13.3 General principles for antiretroviral therapy initiation

13.4 Considerations before initiation of antiretroviral therapy

13.5 Monitoring on the patient on antiretroviral therapy

13.6 Immune reconstitution inflammatory syndrome

13.7 Antiretroviral failure

13.8 Drug interaction

13.9 Antiretroviral drug resistance

13.10 Preexposure prophylaxis

13.11 Postexposure prophylaxis

13.12 Prevention of mother child transmission

References

Chapter 14. Rotavirus and antirotaviral therapeutics: trends and advances

Abstract

14.1 Introduction

14.2 Supportive/symptomatic therapies

14.3 Antiviral drugs/mimetics

14.4 Passive immunotherapy

14.5 Immunotherapeutics

14.6 Immunomodulators

14.7 Cytokines-based therapeutics

14.8 Toll-like receptors-based therapeutics

14.9 Herbal/medicinal plants

14.10 Probiotics

14.11 Advances in drug delivery: nanotechnology-based approach

14.12 Neutraceuticals

14.13 Antioxidants

14.14 Combinational therapy

14.15 Other potential therapeutic approaches

14.16 Conclusion and future prospects

References

Chapter 15. Current therapeutic strategies and novel antiviral compounds for the treatment of nonpolio enteroviruses

Abstract

15.1 Introduction

15.2 Structure and life cycle

15.3 Clinical manifestations

15.4 Antiviral agents

15.5 Advances in vaccine development for HFMD and EV-D68 infections

15.6 Conclusion

References

Chapter 16. Antiviral agents against flaviviruses

Abstract

16.1 Introduction

16.2 Flaviviruses

16.3 Why develop novel antiviral drugs?

16.4 Recent advances in inhibitors targeting flaviviruses

16.5 Conclusion

Acknowledgments

Conflict of interest

References

Chapter 17. Pathophysiology of HIV and strategies to eliminate AIDS as a public health threat

Abstract

17.1 Background

17.2 Natural history of human immunodeficiency virus infection

17.3 Strategies to eliminate human immunodeficiency virus as a public health threat

References

Chapter 18. Herbal drugs to combat viruses

Abstract

18.1 Introduction

18.2 Phytochemicals preventing attachment of virus to host cell

18.3 Phytochemicals preventing penetration and uncoating of viruses

18.4 Phytochemicals inhibiting replication of viral nucleic acids

18.5 Phytochemicals preventing assembly and release of virus

References

Chapter 19. Strategies for delivery of antiviral agents

Abstract

19.1 Introduction

19.2 Classes of antiviral drugs

19.3 The general mechanism of viral infections

19.4 Challenges in the treatment of viral infections

19.5 Combination therapy (fixed-dose combination) for the treatment of viral infections

19.6 Hybrid compounds designed for the treatment of viral infections

19.7 Lipid-based drug delivery systems

19.8 Polymer-based drug delivery system for viral infections

19.9 Conclusion and future perspective

Acknowledgments

References

Chapter 20. Nanovesicles for delivery of antiviral agents

Abstract

Abbreviation

20.1 Introduction

20.2 Overcoming the challenges of traditional delivery of antiviral agents

20.3 Nanovesicles

20.4 Nanovesicles and biomimetic nanovesicles for delivery of antiviral agents

20.5 Conclusion and future prospects

References

Chapter 21. Antiviral biomaterials

Abstract

21.1 Introduction to antiviral biomaterials

21.2 Mechanism of action

21.3 Applications of antiviral biomaterials

21.4 Recent advancements

21.5 Summary/conclusion

Conflict of interest

References

Chapter 22. Antiviral biomolecules from marine inhabitants

Abstract

22.1 Introduction

22.2 Marine polysaccharides

22.3 Other marine polysaccharides as antiviral biomaterials

22.4 Marine peptides as antiviral biomaterials

22.5 Conclusion

Acknowledgment

References

Chapter 23. Plant polysaccharides as antiviral agents

Abstract

23.1 Introduction

23.2 Antiviral mechanisms in polysaccharides

23.3 Plant polysaccharides

23.4 Antiviral activities of plant polysaccharides

23.5 Plant polysaccharide adjuvant for COVID-19 vaccine

23.6 Conclusions and future perspectives

References

Chapter 24. Antiviral peptides against dengue virus

Abstract

24.1 Introduction

24.2 Antiviral peptides targeting dengue virus

24.3 Strategies to identify and develop antiviral peptides against dengue virus

24.4 Direct interactions between antiviral peptides with host cell receptors and enzymes

24.5 Advantages of peptides as antiviral agents

24.6 Limitations of peptides

24.7 Conclusion

Acknowledgments

Disclosure of interest

References

Chapter 25. mRNA vaccines for COVID-19

Abstract

25.1 Introduction

25.2 General advantages associated with messenger RNA vaccines

25.3 General concerns associated with messenger RNA vaccines

25.4 The target viral antigen selection for the COVID-19 messenger RNA vaccines

25.5 Development of the COVID-19 messenger RNA vaccines

25.6 Lipid nanoparticles-mediated delivery of the COVID-19 messenger RNA vaccines

25.7 Vaccine uptake at the injection site and translation at the cellular level

25.8 Immune responses induced by COVID-19 messenger RNA vaccines

25.9 Conclusion

References

Chapter 26. Immunotherapy as an emerging and promising tool against viral infections

Abstract

Abbreviation

26.1 Introduction

26.2 Vaccines

26.3 Antibody-based therapies

26.4 Chimeric antigen receptor T cells immunotherapy

26.5 Defensin therapy

References

Chapter 27. Role of nutraceuticals as immunomodulators to combat viruses

Abstract

27.1 Introduction

27.2 Immunity and its classification

27.3 Virus evasion of the host immune system

27.4 Mechanism of action of nutraceuticals

27.5 Nutraceuticals

27.6 Conclusion

References

Section IV: Others

Chapter 28. In vitro and in vivo approaches for evaluating antiviral efficacy

Abstract

28.1 Introduction

28.2 In vitro approaches

28.3 In vivo assays approaches

28.4 Conclusion

Acknowledgment

References

Chapter 29. Clinical Trials and Regulatory considerations of Antiviral agents

Abstract

Abbreviations

29.1 Introduction

29.2 Classification of antiviral agents

29.3 Clinical trials and Food and Drug Administration in the development of antiviral agents

29.4 The US regulator (Food and Drug Administration)

29.5 Applications submitted to division of antiviral products (US FDA)

29.6 Clinical trials and Food and Drug Administration recommendations for antiherpes viral drugs

29.7 Clinical trials and Food and Drug Administration recommendations for anti-HIV drugs

29.8 Clinical trials and Food and Drug Administration recommendations for Antiinfluenza viral drugs

29.9 Clinical trials and Food and Drug Administration recommendations for Antihepatitis viral drugs

29.10 Clinical trials of herbal molecules as antiviral agents

29.11 Conclusions and future prospects

References

Chapter 30. Future perspectives of antiviral therapy

Abstract

30.1 Introduction

30.2 General classification of antiviral drugs

30.3 Problems and limitations in antiviral drugs

30.4 Modern perspectives in the development approaches of antivirals

30.5 Conclusion

References

Index

Copyright

Academic Press is an imprint of Elsevier

125 London Wall, London EC2Y 5AS, United Kingdom

525 B Street, Suite 1650, San Diego, CA 92101, United States

50 Hampshire Street, 5th Floor, Cambridge, MA 02139, United States

The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, United Kingdom

Copyright © 2023 Elsevier Inc. All rights reserved.

No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions.

This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein).

Notices

Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary.

Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility.

To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein.

ISBN: 978-0-323-91814-5

For Information on all Academic Press publications visit our website at https://www.elsevier.com/books-and-journals

Publisher: Stacy Masucci

Acquisitions Editor: Kattie Washington

Editorial Project Manager: Timothy J. Bennett

Production Project Manager: Selvaraj Raviraj

Cover Designer: Christian J. Bilbow

Typeset by MPS Limited, Chennai, India

List of contributors

Caleb Acquah,     Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada

Nadeesh M. Adassooriya,     Department of Chemical & Process Engineering, University of Peradeniya, Peradeniya, Sri Lanka

Blessing A. Aderibigbe,     Department of Chemistry, University of Fort Hare, Alice, Eastern Cape, South Africa

Yusra Ahmad,     Faculty of Pharmacy, Uttarakhand Technical University, Dehradun, Uttarakhand, India

Ahmed Alfarhan,     Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia

Sibusiso Alven,     Department of Chemistry, University of Fort Hare, Alice, Eastern Cape, South Africa

Mohd Ishtiaq Anasir,     National Institutes of Health (NIH), Ministry of Health Malaysia, Shah Alam, Selangor, Malaysia

Vahid Reza Askari

Department of Pharmaceutical Sciences in Persian Medicine, School of Persian and Complementary Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran

Ishwarya Ayyanar,     Department of Microbiology, Alagappa University, Science Block, Karaikudi, Tamil Nadu, India

Vafa Baradaran Rahimi

Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran

Department of Cardiovascular Diseases, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Samir Bhargava,     Faculty of Pharmacy, DIT University, Dehradun, Uttarakhand, India

Debesh Chandra Bhattacharya,     Department of Microbiology, Vidyasagar University, Midnapore, West Bengal, India

Bhavna,     Faculty of Pharmacy, DIT University, Dehradun, Uttarakhand, India

Buhle Buyana,     Department of Chemistry, University of Fort Hare, Alice, Eastern Cape, South Africa

Debjit Chakraborty,     Division of Epidemiology, ICMR-National Institute of Cholera and Enteric Disease, Kolkata, West Bengal, India

Sambuddha Chakraborty,     Department of Microbiology, Tripura University (A Central University), Suryamaninagar, Tripura West, India

Debprasad Chattopadhyay

ICMR-NICED Virus Unit, ID and BG Hospital, Kolkata, West Bengal, India

ICMR-National Institute of Traditional Medicine, Belagavi, Karnataka, India

Ashwini Chauhan,     Department of Microbiology, Tripura University (A Central University), Suryamaninagar, Tripura West, India

Gollahalli Eregowda Chethan,     Department of Veterinary Medicine, College of Veterinary Science and Animal Husbandry, Central Agriculture University, Aizawl, Mizoram, India

H. Chitme,     Faculty of Pharmacy, DIT University, Dehradun, Uttarakhand, India

Manuele Figueiredo da Silva,     Institute of Pharmaceutical Sciences, Federal University of Alagoas, Maceió, Brazil

Edeildo Ferreira da Silva-Júnior,     Institute of Chemistry and Biotechnology, Federal University of Alagoas, Maceió, Brazil

Michael K. Danquah,     Department of Chemical Engineering, University of Tennessee, Chattanooga, TN, United States

Aparajita Dasgupta,     Department of Preventive and Social Medicine, All India Institute of Hygiene and Public Health, Kolkata, West Bengal, India

Regina Sharmila Dass,     Fungal Genetics and Mycotoxicology Laboratory, Department of Microbiology, School of Life Sciences, Pondicherry University, Pondicherry, India

Ujjwal Kumar De,     Division of Medicine, ICAR-Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, India

João Xavier de Araújo-Júnior

Institute of Chemistry and Biotechnology, Federal University of Alagoas, Maceió, Brazil

Institute of Pharmaceutical Sciences, Federal University of Alagoas, Maceió, Brazil

Kuldeep Dhama,     Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, India

Ranjithkumar Dhandapani,     Chimertech Private Limited, Chennai, Tamil Nadu, India

Amal Kumar Dhara,     Department of Pharmacy, Contai Polytechnic, Purba Medinipur, West Bengal, India

Ana Beatriz Souza Flor dos Santos,     Institute of Pharmaceutical Sciences, Federal University of Alagoas, Maceió, Brazil

Ibrahim M. El-Sherbiny,     Nanomedicine Research Laboratories, Center for Materials Science, Zewail City of Science and Technology, 6 of October City, Giza, Egypt

Zizo Feketshane,     Department of Chemistry, University of Fort Hare, Alice, Eastern Cape, South Africa

Jitendra Singh Gandhar,     Division of Medicine, ICAR-Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, India

Suman Ganguly,     West Bengal State AIDS Prevention and Control Society, Kolkata, West Bengal, India

Tomás M. Grosso

Laboratory of Immunology, National University of Luján, Buenos Aires, Argentina

Clinical Trials Unit, Huésped Foundation, Buenos Aires, Argentina

Sunandha Jeeva Bharathi Gunasekaran,     Department of Microbiology, Alagappa University, Science Block, Karaikudi, Tamil Nadu, India

Mayuri Gupta,     Faculty of Pharmacy, DIT University, Dehradun, Uttarakhand, India

Pradip Kumar Jana,     Virus Research and Diagnostic Laboratory, ICMR-National Institute of Cholera and Enteric Diseases, Kolkata, West Bengal, India

Ali H. Karaly,     Nanomedicine Research Laboratories, Center for Materials Science, Zewail City of Science and Technology, 6 of October City, Giza, Egypt

Sandhya Khunger,     Department of Microbiology, Faculty of Allied Health Sciences, Shree Guru Gobind Singh Tricentenary University, Gurugram, Haryana, India

Vuyolwethu Khwaza,     Department of Chemistry, University of Fort Hare, Alice, Eastern Cape, South Africa

Maame A. Korsah,     Department of Mathematics, University of Tennessee, Chattanooga, TN, United States

Michelle Felicia Lee,     Centre for Virus and Vaccine Research, School of Medical and Life Science, Sunway University, Bandar Sunway, Selangor, Malaysia

Nadun H. Madanayake,     Department of Botany, University of Peradeniya, Peradeniya, Sri Lanka

Agniva Majumdar,     Virus Research and Diagnostic Laboratory, ICMR-National Institute of Cholera and Enteric Diseases, Kolkata, West Bengal, India

Yashpal Singh Malik,     College of Animal Biotechnology, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana, Punjab, India

Keshab C. Mandal,     Department of Microbiology, Vidyasagar University, Midnapore, West Bengal, India

Zintle Mbese,     Department of Chemistry, University of Fort Hare, Alice, Eastern Cape, South Africa

Bulu Mohanta,     Department of Pharmacology, Seemanta Institute of Pharmaceutical Sciences, Jharpokharia, Mayurbhanj, Odisha, India

Joy Mondal

ICMR-NICED Virus Unit, ID and BG Hospital, Kolkata, West Bengal, India

Department of Microbiology, Vidyasagar University, Midnapore, West Bengal, India

Igor José dos Santos Nascimento,     Institute of Chemistry and Biotechnology, Federal University of Alagoas, Maceió, Brazil

Amit Kumar Nayak,     Department of Pharmaceutics, Seemanta Institute of Pharmaceutical Sciences, Jharpokharia, Odisha, India

Ram Gopal Nitharwal,     Department of Biotechnology, Central University of Haryana, Mahendergarh, Haryana, India

Xhamla Nqoro,     Department of Chemistry, University of Fort Hare, Alice, Eastern Cape, South Africa

Benil P.B.,     Department of Agadatantra, Vaidyaratnam P.S. Varier Ayurveda College, Kottakkal, Kerala, India

Babul Rudra Paul,     Division of Medicine, ICAR-Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, India

Sijongesonke Peter,     Department of Chemistry, University of Fort Hare, Alice, Eastern Cape, South Africa

Chit Laa Poh,     Centre for Virus and Vaccine Research, School of Medical and Life Science, Sunway University, Bandar Sunway, Selangor, Malaysia

Yasmine Radwan,     Nanomedicine Research Laboratories, Center for Materials Science, Zewail City of Science and Technology, 6 of October City, Giza, Egypt

Rajakrishnan Rajagopal,     Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia

Saikishore Ramanthan,     Medical Microbiology Unit, Department of Microbiology, Alagappa University, Karaikudi, Tamil Nadu, India

Akila Ravindran,     Department of Microbiology, Alagappa University, Science Block, Karaikudi, Tamil Nadu, India

Ryan Rienzie,     Department of Agricultural Biology, Faculty of Agriculture, University of Peradeniya, Peradeniya, Sri Lanka

Érica Erlanny S. Rodrigues

Institute of Chemistry and Biotechnology, Federal University of Alagoas, Maceió, Brazil

Institute of Pharmaceutical Sciences, Federal University of Alagoas, Maceió, Brazil

Vrenda Roy,     Department of Indian System of Medicine, Government of Kerala, Kerala, India

Jagannath Sahoo,     Faculty of Pharmacy, DIT University, Dehradun, Uttarakhand, India

Varun Kumar Sarkar,     Division of Medicine, ICAR-Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, India

Anamika Sengupta,     Department of Health Science Education & Pathology, College of Medicine, University of Illinois, Peoria, IL, United States

Neeraj Sethiya,     Faculty of Pharmacy, DIT University, Dehradun, Uttarakhand, India

Leandro Rocha Silva,     Institute of Chemistry and Biotechnology, Federal University of Alagoas, Maceió, Brazil

Srishti Soni,     Division of Medicine, ICAR-Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, India

Omar Sued,     Pan American Health Organization, Washington, DC, United States

Angeline Jessika Suresh,     Fungal Genetics and Mycotoxicology Laboratory, Department of Microbiology, School of Life Sciences, Pondicherry University, Pondicherry, India

Subidsha Suyambu Krishnan,     Department of Microbiology, Alagappa University, Science Block, Karaikudi, Tamil Nadu, India

Sathiamoorthi Thangavelu,     Medical Microbiology Unit, Department of Microbiology, Alagappa University, Karaikudi, Tamil Nadu, India

Jacob Thomas,     Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia

Shalini Upadhyay,     A.S.J.S.A.T.D.S. Medical College, Fatehpur, Uttar Pradesh, India

Navraj Upreti,     Faculty of Pharmacy, DIT University, Dehradun, Uttarakhand, India

Balasubramanian Vellaisamy,     Department of Microbiology, Alagappa University, Science Block, Karaikudi, Tamil Nadu, India

Palanivel Velmurugan,     Center for Materials Engineering and Regenerative Medicine, Bharath Institute of Higher Education and Research, Chennai, Tamil Nadu, India

Viroj Wiwanitkit,     Dr DY Patil University, Pune, Maharashtra, India

Roghayeh Yahyazadeh,     Departments of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Sora Yasri,     Private Academic Consultant Center, Bangkok, Thailand

Preface

Amal Kumar Dhara and Amit Kumar Nayak

Once virus infection is established, antiviral therapy is the only option to control the infection. In principle, all the steps in the virus life cycle ranging from entry to release can be explored as molecular targets for antiviral therapy. Thus, antiviral therapy is one of the most exciting aspects of virology, since it has successfully employed basic science to generate very effective treatments for serious viral infections. In fact, the vast majority of antiviral drugs developed since the 1980s. These antiviral drugs block diverse steps of the viral life cycle, including entry, reverse transcription, viral protein processing, and integration of various viruses causing influenza, herpes, hepatitis, AIDS, COVID, etc. In this regard, the current book entitled Viral Infections and Antiviral Therapies aims to provide a thorough insight into the comprehensive and up-to-date trends of antiviral therapeutics and its mechanisms. This book contains four sections with 30 chapters and presents a systematic discussion on various key topics about viral infections and transmissions, antiviral agents, and therapeutics by some of the leading expert academicians and researchers around the globe. A concise and snappy account on the contents of each chapter has been described to make available a glimpse of the book to the readers.

Section I contains Chapter 1 that presents introductory overviews of viral infections, transmission, and management of viral infections by using various antiviral agents.

Section II contains seven chapters. Chapter 2 describes various important emerging viral diseases, namely ebola virus, dengue virus, chikungunya virus, West Nile virus, zika virus, yellow fever virus, nipah virus, influenza virus, and corona viruses. In addition, the ever changing landscape of infectious diseases, factors affecting emergence of viral diseases, prevention, and control of viral diseases have been addressed in this chapter. Chapter 3 provides a comprehensive understanding of various genetic and ecological changes and their effects on viral evolution through various approaches and different modes of transmission of viruses. Chapter 4 summarizes the modes of viral infections and transmissions. This chapter covers epidemiological triad and viral infection, transmission of viral infections, and various modes of transmission of viral infections. Chapter 5 analyzes SARS-CoV-2, its transmission, impact, varied intervention to mitigate its spread, the potential dynamics of similar pandemics, and recommendations for future studies. Chapter 6 discusses about various common sexually transmitted diseases caused by viral infections are genital warts, genital herpes and human immuno-deficiency virus, human T-cell lymphotropic virus, hepatitis A, B, and C. Additionally, prevention of sexually transmitted viral infections has been addressed in this chapter. Chapter 7 overviews various diagnostic modalities and developments in this field that may augment our decision-making capacity for best possible modality to be used in future. This chapter covers the purpose of laboratory diagnosis of viral infections, sample collection, packaging, and transport of collected samples for testing, and methods in diagnostic virology including virus isolation, direct microscopy, detection of viral antigens and antibody (serology), and molecular techniques. Chapter 8 elaborates on the electron microscopy as diagnostic tool in virology and its structure and functions. In addition, preparation of biological specimens for analyses by electron microscopy has been discussed.

Section III contains 19 chapters. Chapter 9 focuses on recent advancements and clinical trials underway in the past 5 years from 2016 to 2021 explaining various strategies employed by using oncolytic viruses as therapeutic sources to combat the most common forms of cancer. Chapter 10 addresses comprehensive discussions involving the significant development of antiviral drugs against the most challenging viruses that humankind has faced. In addition, aspects associated with the perspective of medical need, technical possibilities, and economic restrictions have been covered. Chapter 11 highlights about the antiviral agents currently available in the market as well as those under clinical trials, emphasizing their antiviral mechanisms. In addition, the chapter gives an outline of compounds that are in the research stage, focusing on phytochemicals that are currently being studied for their efficacy to combat influenza. Chapter 12 not only focuses on currently FDA approved antiherpes virus agents but also reveals the prospects of ethnomedicines, which will be the major lead molecules in the development of new antiherpes virus agents in near future. Chapter 13 deals with a comprehensive discussion on antiretroviral therapies. This chapter covers commonly used ART drugs and formulation of antiretroviral treatment, general principles for antiretroviral therapy initiation, considerations before initiation of antiretroviral therapy, monitoring on the patient on antiretroviral therapy immune reconstitution inflammatory syndrome (IRIS), antiretroviral failure, drug interaction, antiretroviral drug resistance, pre- and postexposure prophylaxis, and prevention of mother child transmission. Chapter 14 discusses on the trends and advances in the specific therapeutic approaches being targeted against rotavirus This chapter highlights various therapies including fluid therapy, immune-therapies, probiotics, phytoconstituents, antioxidants, etc. Chapter 15 demonstrates researches focusing on novel therapeutic interventions for nonpolio enteroviruses that have emerged as a growing concern in the past decade. Chapter 16 highlights recent progress in medicinal chemistry field focused on relevant compounds, as antiviral agents against flaviviruses. In addition, related molecular modeling, virtual screening, drug repurposing, and biological evaluations have been covered. Chapter 17 addresses the backgrounds of HIV and AIDS, epidemiology, transmission and establishment of HIV infection, HIV life cycle, physiopathogenesis, response to HIV infection, natural history of HIV infection, transmission routes, manifestation of acute HIV infection, laboratory diagnosis, antiretroviral treatment, and various effective strategies to eliminate HIV as a public health threat. Chapter 18 explores important drug targets for curbing viral infections with phytochemicals derived from medicinal plants (herbal drugs). This chapter covers phytochemicals preventing attachment of virus to host cell, phytochemicals preventing penetration and uncoating of viruses, phytochemicals inhibiting replication of viral nucleic acids and phytochemicals preventing assembly and release of virus. Chapter 19 reports the efficacy of hybrid molecules, drug delivery systems incorporated with antiviral agents, and metal-based nanoparticles in the treatment of viral infections, such as HIV, herpes, hepatitis, Ebola, human papillomavirus, viral pneumonia, common cold, COVID-19, and Middle East respiratory syndrome. Chapter 20 expounds on the research and application of nanovesicles for delivery of antiviral agents to attack viral infections such as influenza, HIV, and the most recent COVID-19. Highlights on antiviral monotherapies, currently approved or still undergoing clinical investigations and future perspectives aiming to translate the outstanding research outcome into clinical settings have also been discussed. Chapter 21 presents an overview and better understanding of the current knowledge in the arena of antiviral biomaterials. In addition, the chapter illustrates the multidisciplinary approaches of antiviral biomaterials in terms of applications, recent advancements, and challenges associated with antiviral biomaterials. Chapter 22 mainly focuses on the antiviral benefits of most commonly reported marine polysaccharides such as chitin, chitosan, carrageenan, alginate, etc., and marine-based peptides as antiviral biomaterials. Chapter 23 explores antiviral activities of various plant polysaccharides. The antiviral mechanisms of polysaccharides (of different sources like plant, animal, marine, etc.) and their derivatives have been summarized in the current chapter with the goal of providing a sound platform for future research on the antiviral properties of plant polysaccharides and their chemically modified derivatives. Chapter 24 highlights the current status of development of antiviral peptides targeting dengue virus, strategies that were utilized to design antiviral peptides, interactions that were identified between antiviral peptides and dengue virus host cell receptors or enzymes, advantages and disadvantages of antiviral peptides, as well as potential ways to overcome their limitations. Chapter 25 summarizes the history of development and delivery of these two mRNA vaccines with emphasis on crucial aspects of design strategy, delivery approach, and their noteworthy roles in inducing immune responses postvaccination. Chapter 26 explains some of the unique existing approaches to prevent and treat viral infectious disease via immunotherapies, such as mAb-based therapies, vaccines, T-cell-based therapies, utilizing cytokine levels, and checkpoint inhibition as well as defensins. Chapter 27 discusses the potential role of nutraceuticals as immunomodulators in combating viral infections. The chapter covers immunity and its classification, virus evasion of the host immune system, mechanism of action, definition, classifications, and immunomodulatory actions of nutraceuticals against viruses.

Section IV contains three chapters. Chapter 28 insights into both in vitro and in vivo approaches that are generally employed to test efficacy of new antiviral drugs. Chapter 29 provides a collected evidence of the undergoing clinical trials on different types of antiviral agents or their combinations. The discussion and recommendations for new molecules approved by the FDA (2015–21) have been included. Chapter 30 discusses the general developments with the antivirals along with the modern perspectives for which these compounds can usher better and holistic therapeutic approaches utilizing state-of-the-art technology, software, and related tools in an omics era.

We, the editors, sincerely convey our thanks to all the distinguished authors for their invaluable contributions of quality chapters in a timely manner. This book could not have been published without cooperation and wholehearted supports of Elsevier, Inc., Andre Gerhard Wolff, Kattie Washington (Acquisitions Editor), Timothy Bennett (Editorial Project Manager), and Selvaraj Raviraj (Production Manager) in the book-editing process. We would like to express our sincere thanks to Dinesh Natarajan (Copyright Coordinator) for their outstanding support in obtaining copyright permissions. All copyright contents and reprinting licenses from different copyright sources have duly been gratefully acknowledged. Finally, we must appreciate our family members, friends, colleagues, and students for their continuous encouragements, inspirations, and moral supports during the book-editing process. We will be extremely happy along with our contributing authors and publishers, if our efforts fulfill the needs of the students, researchers, academicians, and others.

Section I

Introduction

Outline

Chapter 1 Introduction to antiviral therapy

Chapter 1

Introduction to antiviral therapy

Amal Kumar Dhara¹ and Amit Kumar Nayak²,    ¹Department of Pharmacy, Contai Polytechnic, Purba Medinipur, West Bengal, India,    ²Department of Pharmaceutics, Seemanta Institute of Pharmaceutical Sciences, Jharpokharia, Odisha, India

Abstract

Viruses are acellular obligate intracellular parasites that can infect humans, plants, animals, yeast, bacteria, protozoa, archaea, as well as other viruses. Transmission of viruses takes place in a variety of ways. Some viruses are transmitted through touch, air, and saliva and others are transmitted by insects (e.g., mosquitoes), sexual contact, sharing contaminated needles/blood, contaminated water and food, etc. Viral infections are managed either by antiviral vaccines or by using suitable antiviral drugs or they can also be controlled using phytomedicines. The present chapter provides an overview of viral infections and their transmission and management using various antiviral agents.

Keywords

Viral infections; viruses; transmission; antiviral agents; antiviral therapy

1.1 Introduction

The current COVID-19 pandemic, caused due to SARS-CoV-2 virus, once again proved that viruses are still a mystery and human beings could be helpless before finding the treatment. Viruses are acellular obligate intracellular parasites that can infect humans, plants, animals, yeast, bacteria, protozoa, archaea, as well as other viruses [1,2]. For multiplication, they require host cells [3]. Viruses are unique as they are alive and can multiply only in living host cells [4]. Viruses are highly complex in producing diseases [5,6]. They consist of nucleic acids deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) covered by a capsid (a protein coat) [7]. The combination of capsid and genome is known as nucleocapsid [8]. Envelope surrounding the nucleocapsid is also found in viruses as an additional component [7,8]. Spike proteins are one of the most important structural features of viruses, which bind to specific receptors of the host cell and cause infections [9]. Some viruses also contain viral enzymes that can cause infection to the host cell. Viruses with all the essential components required to infect the host cell are called virions [7,10]. There are two categories of viruses: DNA viruses and RNA viruses, depending on their replication by using DNA or RNA, respectively [7]. Examples of DNA viruses include adenoviruses, herpes viruses, etc., and RNA viruses include hepatitis C virus (HCV), influenza virus, human immunodeficiency virus (HIV), SARS-CoV-2, etc.

1.2 Virus replication cycle

To replicate, a virus makes use of cell and viral replication cycle that leads to extensive structural and biochemical changes in the infected host cell [11]. Cells infected by virus may die due to lysis or apoptosis and by the release of virions [10,11]. The observed symptoms caused by viral diseases are due to immune response to the virus. There are some variations in replication cycle of viruses; however, in most cases there are five steps in the viral replication cycle [10–12] (Fig. 1.1):

1. Attachment

2. Penetration

3. Synthesis

4. Assembly

5. Release.

Figure 1.1 Virus replication cycle.

Attachment: Without a host cell, viruses are inactive metabolically. The attachment of the virus to a receptor of host cell is highly specific, just like lock and key system [12]. Due to this specificity, a particular virus can infect only a particular cell type.

Penetration or entry: In case of bacteriophage (virus that infects bacteria), nucleic acid enters the host cells and leaves the capsid outside of the cell [13]. In case of eukaryotic viruses, the entire capsid enters the host cell [14,15]. Viruses also enter the cell by endocytosis, when capsid is engulfed by the host cell [16]. Once virus enters the cell, the virus nucleic acid is released due to degradation of viral capsid and finally becomes available for replication as well as transcription [17,18].

Synthesis: This is directed by the viral genome. RNA viruses synthesize mRNAs and viral genomic RNAs usually by using RNA core as a template [19,20]. DNA viruses make mRNAs by using host cell protein and enzymes through direct protein synthesis [21].

Assembly: The capsid is composed of different types of proteins, whose numbers are varied (3–60) [22,23]. Fewer the number of proteins involved, simple is the virus. The different types of proteins are arranged in a specified order.

Release: At the end of replication, most of the viruses lyse host cell and as a result, new virions are released [18]. Budding is another process, common in enveloped viruses, where one virus is released at a time through the membrane without lysis of the cell [24].

1.3 Virus transmission and types of viral infections

Transmission of viruses takes place in a variety of ways [25]. Some viruses are transmitted through touch, air, saliva, and others are transmitted by insects (e.g., mosquitoes), sexual contact, sharing contaminated needle/blood, contaminated water, food, etc. [26,27]. There are various important modes of viral transmission:

1. Vertical transmission: In this mode, transmission of pathogens occurs from mother to child either before or after childbirth [28–30]. The vertically transmitted viruses include HIV, Zika, etc.

2. Transmission through breast milk: During breast feeding, the pathogens may be transmitted and cause infantile viral infection [31–33]. Example of viruses transmitted via breast milk include HIV, cytomegalovirus (CMV), and human T-cell lymphotropic virus.

3. Transmission via respiratory tract: This is the most common mode of viral transmission that leads to a number of viral infections [34]. Very recent example is COVID-19. The surrounding environment is very important for transmission of viruses via respiratory contact. Droplet transmission (during sneezing, talking, etc.) and airborne transmission are the major causes of transmission [26].

4. Transmission caused by transplantation: This is caused by transplantation of organ obtained from infected donor (living or dead) [35,36]. The viruses transmitted via transplantation include hepatitis B virus (HBV), HCV, and HIV.

5. Transmission via blood and blood transfusion: Viral pathogens may transmit with plasma or cellular components of blood, for example, HIV. Other examples include HBV, HCV, HGV, etc. [37,38].

6. Transmission via vector: Some animals, mainly insects like mosquitoes (from infected host to non-infected host), act as vectors for viral transmission [39–41]. Examples of vector-borne transmission of viral infections are Zika virus (ZIKV), Chikungunya, etc.

7. Transmission via sexual contact: Sexual contact (more specifically sexual intercourse) is also another important cause of transmission of viral infection, such as HIV, HBV, HCV, ZIKV infection, etc. [42,43].

8. Foodborne and waterborne transmission: Food and drinks can also transmit viral infections, which have been the case recently in SARS-CoV-2 [44–46].

9. Orofecal transmission: Transmission of virus through feces due to poor sanitation and improper hand washing may cause viral infections, for example, polio virus and hepatitis virus infection [47–49].

10. Transmission via eye, skin, and mucosal contact: Herpes simplex, human papilloma, and molluscum contagiosum can be transmitted via skin contact [50–52]. Adenovirus and SARS-CoV-2 are also transmitted by hand-to-eye contact [6,43].

Different types of viral infections include:

1. Respiratory viral infections: These are the most common viral infections. The organs affected are nose, throat, lungs, and upper respiratory tract [53,54]. These spread from one person to other by inhaling droplets (containing viruses) [26]. The examples of various respiratory viral infections are [53–58] (a) Respiratory syncytial virus—both upper and lower respiratory tract infection. (b) Rhinovirus—usual symptoms of common cold include sneezing, coughing, sore throat, mild headache, etc. (c) Seasonal influenza—every year certain percentage of people suffer from this illness and the symptoms are usually more severe than common cold, including fatigue, mild fever, aches throughout the body, etc. (d) SARS-CoV-2—this is popularly known as COVID-19, as the infection started to spread during the November 2019 and in 2020, it led to a pandemic. Millions of people across the globe died due to this severe acute respiratory syndrome. Common symptoms of SARS-CoV-2 infection include fever, cough, shortness of breath, and pneumonia [56].

2. Viral skin infection: The skin is affected due to infections such as [50–52,58]: (a) Herpes simplex virus-1 (HSV-1)—this can usually be transmitted through saliva during kissing, sharing of lip balm, or by infected food sharing. (b) Molluscum contagiosum—it is another type of skin infection, usually observed in children (age group: 1–10 years) and there is appearance of small white- or pink-colored bumps on the skin anywhere on the body, including neck, face, abdomen, legs, arms, etc. (c) Varicella-zoster virus (VZV)—it is a DNA virus that causes chicken pox. This virus causes fatigue, itchy and oozing blisters along with high fever.

3. Sexually transmitted viral infections: Infections spread through body fluid contact and also through blood. Different sexually transmitted viral infections include [43,59–61]: (a) HIV—these viruses attack the immune system of the body and are transmitted via semen, vaginal fluid, and infected blood. The symptoms of AIDS include fever, weight loss, fatigue, and recurrent infections (due to deficiency of immunity). The incidence of HIV infection can be reduced by avoiding sexual activity with unknown partners, testing blood for HIV before transfusion, and using unused/sterile needle for injection of drugs. (b) Genital herpes—it is caused by herpes simplex virus-2 (HSV-2) and is a very common sexually transmitted infection. The symptoms of HSV-2 include itching, pain, (on the penis or vagina), and small sores. To avoid HSV-2 infection, person should abstain from vaginal, anal, and oral sex (with the partners having HSV-2 infection).

4. Viral hepatitis: Viral hepatitis is caused by different viruses including hepatitis A, B, C, D, and E [62]. In this infection, liver is damaged due to inflammation. Various symptoms of viral hepatitis include fever, loss of appetite, fatigue, abdominal pain, dark urine, nausea, vomiting, etc. [63,64]. Viral hepatitis is transmitted through contaminated water, food, or via body fluids and blood. Hepatitis A and E are transmitted, when a person ingests contaminated food or water (usually contamination comes through fecal matter from infected person). Hepatitis B and C are transmitted through blood and body fluids, which cause acute and chronic hepatitis. Newborn baby can also be infected with hepatitis B and C during childbirth transmitted from mother. Sex with infected person, transfusion of infected blood, equipment sharing like needles, syringes, etc., can also cause hepatitis B and/or C viral infections [62].

5. Viral gastroenteritis: A number of different viruses, including rotaviruses, noroviruses, adenoviruses, sapoviruses, and astroviruses, are responsible for viral gastroenteritis [63]. Vomiting, diarrhea, headache, abdominal pain, fever, etc., are the main symptoms of such infection and is also known as stomach flu [65,66]. The above viruses can be transmitted through contaminated water, foods, beverages, and close contact with the infected person and touching contaminated utensils or surfaces. Contamination of food and water is usually caused by sewage, persons (having viral gastroenteritis) engaged in food production and handling, and poor hygienic condition. Rotavirus usually affects young children as well as infants. Children or infants suffer from severe diarrhea, vomiting, and anorexia [66,67]. Norovirus can affect a person of any age and is highly contagious [68,69]. It is transmitted through contaminated water, foods, and also by an infected person. Diarrhea, fever, body aches are the common symptoms. Adenovirus can also affect anyone and is usually transmitted through coughing, sneezing, and by touching contaminated surfaces or objects [70]. Symptoms of adenovirus infection include fever, coughing, bronchitis, sore throat, runny nose, pink eye, etc. Astrovirus usually affects children and observed symptoms include diarrhea, mild dehydration, headache, stomach pain, etc. [71,72].

6. Flavivirus infection: Flaviviruses include ZIKV, West Nile virus (WNV), Dengue virus (DENV), Japanese encephalitis virus (JEV), etc., and belong to Flaviviridae family [73,74]. These viruses usually spread in underdeveloped countries and more commonly among the poor. Different flaviviruses produce varieties of symptoms and represent major threat to human health resulting in high morbidity and mortality rates. The transmission of flaviviruses occurs by mosquitoes, ticks, person-to-person, and also by vertical transmission, that is, mother to child in pregnant women. The symptoms of ZIKV are microcephaly in newborn and malformation of fetus in pregnant mother [75,76]. The other symptoms include congenital abnormalities like cerebral palsy, epilepsy, intellectual disability and also, audio-visual and behavioral disturbances. The symptoms of WNV include headache, fever, myalgia, rash, lymphadenopathy, gastrointestinal disorders, and also meningitis and encephalitis [77,78]. The symptoms associated with DENV include mild fever, severe hemorrhagic fever, and dengue shock syndrome [79,80].

1.4 Antiviral agents

Antiviral agents are drugs used for the control and treatment of viral infections [81]. A schematic presentation of the management of viral infection with antiviral agents is given below (Fig. 1.2) [81–86]:

Figure 1.2 Antiviral agents for the managements of viral infections.

On the basis of viral infection, antiviral drugs are categorized into following groups [82,85–89]:

1. Antiherpes virus agents

2. Anti-HIV agents

3. Antiviral drugs used for the treatment of hepatitis

4. Anti-influenza agents

5. Antirotavirus agents

6. Antiviral agents against enteroviruses

7. Antiviral agents against flaviviruses

8. Antiviral agents used for the treatment of respiratory infection.

1.4.1 Antiherpes virus agents

These drugs are effective against herpes virus (DNA viruses) like HSV-1, HSV-2, Epstein Barr virus (EBV), VZV, CMV, Roseolo virus, Kaposi’s sarcoma-associated virus, etc. [90–92]. Like all other viral infections, these can also be managed by minimizing the risk of infection, vaccination, and suitable antiviral agents. The varieties of anti-herpes virus agents available in the market with varying clinical efficacy are presented in Table 1.1.

Table 1.1

1.4.2 Anti-HIV agents

HIV is a typical retrovirus and a single-stranded RNA virus [93–96]. Two major forms of HIV are HIV-1 (widely distributed and found worldwide) and HIV-2 (it is most common in western Africa). Emphasis should be given on prevention of transmission of diseases. Different antiviral drugs are available for the treatment of AIDS, which are shown in Table 1.2.

Table 1.2

1.4.3 Antiviral drugs used for the treatment of hepatitis

Hepatitis cause damage to the liver due to inflammation, resulting in impairment of liver function [48]. Inflammatory disorders of liver (hepatitis) may be acute or chronic. There are five types of hepatitis. Hepatitis A caused by hepatitis A virus (HAV), similarly hepatitis B, hepatitis C, hepatitis D, and hepatitis E are caused by HBV, HCV, hepatitis D virus, and hepatitis E virus, respectively [48,62]. Out of these five types, HAV, HBV, and HCV are very common and clinically significant. Several important antiviral drugs as well as vaccines are available in the market for treating hepatitis [97–99].

Hepatitis A: Hepatitis A is caused by HAV. It is not a chronic liver disease, but some complications may occur in the person infected with HAV [100]. Prevention is the main approach of infection control, as there is no specific antiviral drug available [101]. However, for prevention, hepatitis vaccine can be recommended.

Hepatitis B: HBV produces one of the most serious health problems till now and the annual deaths due to HBV infection is over 1 million [102,103]. The therapeutic approach is the suppression of replication of HBV and improvement of quality of life. Lamivudine is widely used, low-cost, and well-tolerated drug, which acts by inhibiting viral polymerase/reverse transcriptase [104,105]. The antiviral drugs used to treat HBV infection include telbivudine, entecavir, adefovir dipivoxil, tenofovir disoproxil, etc. [97,102,105,106]. Interferon-based therapy (recombinant and lymphoblastoid IFN-α) has also been exhibited significant activity in chronic hepatitis B (CHB) infection [107,108]. Inhibition of HBV life cycle is another important strategy in controlling HBV infection. The different HBV life cycle inhibitors include inhibitor of HBV DNA polymerase (e.g., lagociclovir), viral entry inhibitor (e.g., Myrcludex-B), cccDNA synthesis inhibitor, inhibitor of nucleocapsid assembly, etc. [105–109]. Immunomodulators also play a significant role in CHB treatment [110].

Hepatitis C: HCV infection is usually asymptomatic or mildly symptomatic and thus its diagnosis is difficult [111]. Chronic HCV infection causes serious liver problems, including cirrhosis or hepatocellular carcinoma. Chronic HCV must be treated as early as possible [112,113]. List of some important drugs are mentioned in Table 1.3.

Table 1.3

1.4.4 Anti-influenza agents

In general, there are three types influenza viruses: Influenza viruses A, B, C, and D are found in diseased pigs [114]. Out of these, influenza viruses A and B infect human beings [115]. In the past, influenza pandemic was observed in 1918 as Spanish flu [116], in 1957 Asian flu [117], in 1968 Honk Kong flu [118], and in 2009 swine flu [119]. Due to these pandemics, millions of lives were lost and severe socioeconomical damage occurred. The anti-influenza viral agent are classified as follows [120–123]:

1. Matrix protein Z ion channel inhibitors, for example, Amantadine, Rimantadine.

2. Neuraminidase inhibitors, for example, Zanamivir, Oseltamivir, Peramivir, Laninamivir.

3. RNA-dependent RNA polymerase (RdRp) inhibitor, for example, Favipiravir.

4. Polymerase acidic protein cap-dependent endonuclease inhibitor, for example, Bloxavir marboxil.

5. Hemagglutinin (HA) inhibitor/Fusion inhibitor (HA is a glycoprotein found in envelope of influenza virus, which plays important role in the process of viral binding, fusion, and entry), for example, Umifenovir or Arbidol.

Some anti-influenza agents, obtained from traditional medicinal plants, have played important role in the management of influenza virus infection [124,125]. Some important examples of such plants include Cephalotaxus harringtonia (NA inhibitor) [126], Glycyrrhiza uralensis (NA inhibitor) [127], Echinaceae purpurea (HA inhibitor) [128], Sanicula europaea (RdRp inhibitor) [129], etc. Among the several antiviral drugs, vaccines are the very important agents to prevent influenza virus. Both live attenuated and inactivated vaccines are available in the market.

1.4.5 Antiviral agents against flavivirus

More than 70 viruses belong to genus Flavivirus, including DENV, ZIKV, Yellow fever virus, JEV, WNV, etc. [74]. Dengue fever is mosquito-borne disease caused by DENV and spreads very fast [130]. In 2007, ZIKV outbreak was reported in Micronesia [131]. No specific agents are available for the treatment of flavivirus infections. Several research works across the globe are being conducted to obtain a novel antiviral agent(s), which target the different stages in replication cycle.

Much research has already been done as well as is ongoing to find out suitable antiviral agents that can be used for the treatment of dengue [130,132]. Unfortunately, neither directly acting antivirals (DAA) nor host directed antivirals have shown clinical significance. Clinical trials of balapiravir, a DAA, failed to exhibit significant efficacy as compared to placebo [133]. A group of researchers studied narasin, a novel antiviral agent effective against DENV [134]. The investigational results suggested that narasin caused inhibition of DENV replication (in vitro), however, further studies are needed to establish narasin as a potential anti-DENV agent.

1.5 Antiviral agents obtained from plant sources

Like ancient people, people nowadays also show the tendency to use herbal drugs for treatment of a variety of diseases [125–129]. A plethora of valuable phytochemicals is available. During the present pandemic (COVID-19) situation, scientists put in their sincere efforts to find out novel antiviral drug(s) or agents that can be used as an adjuvant therapy or as an immunomodulator to combat viral infections [126,135].

The different phytoconstituents exhibited their activity in different stages of virus replication cycle:

1. Some potential phytochemicals prevent attachment of virus to host cell. Examples include loliolide obtained from Phyllanthus urinaria that caused inhibition of attachment to the host cell of HCV [136]. Ginsenosides from Panax quinquefolium prevent attachment of influenza A H1N1 to the host cell receptors [137]. Quercetagetin also exhibited significant activity by inhibiting chikungunya virus attachment to host cell [138].

2. Phytoconstituents prevent penetration and uncoating of viruses. Withanone, an important constituent obtained from Withania somnifera, interferes with the entry of SARS-CoV-2 [139]. Epigallocatechin gallate caused inhibition of viral entry and showed activity against ZIKV (Mr766 strain) [140]. Jatrophane esters from Euphorbia dendroides latex showed antiviral activity against replication of chikungunya virus [141]. Aqueous extract of bark of Azadirachta indica prevented the entry of HSV-1 into the host cell [142].

3. Phytochemicals caused inhibition of viral nucleic acid replication. In a study, C. D. Lee and his coworkers observed that Phyllanthus amavus may be used as a potential antiviral agent in the treatment of HBV. The plant caused downregulation of the DNA replication of HBV [143]. Lignan, an important constituent of Chinese plant Radix, caused disruption of replication machinery in respiratory syncytial virus [144].

4. Phytoconstituents caused prevention of assembly and release of virus. Kaempferol from Ficus benjamina significantly inhibited HSV-1, HSV-2, and coronavirus by interfering their release via 3a channel inhibition [145]. In a study, it was reported that naringenin showed antiviral activity by impairing the assembly of virion of ZIKV [146].

1.6 Antiviral vaccines

Vaccines play an important role in the effective control and prevention of viral infections. Polio and small pox eradication are ideal examples that guided researchers in the development of vaccines for prevention and control of different types of viral infections [147,148]. Later, many vaccines like measles, mumps, rubella, diphtheria, pertusis, tetanus, BCG., etc., vaccines were developed [149]. The most important objective for developing antiviral vaccines is the development of immunity, which resembles natural immunity for lifelong [150]. Examples of some antiviral vaccines available in the market are mentioned in Table 1.4.

Table 1.4

Various types of antiviral vaccines have been developed:

1. Live viral vaccines: These are developed from virus strains but are attenuated [151]. They are able to replicate in the host cell and thus boosting immunity, for example, polio virus vaccine.

2. Inactivated vaccines: Whole particles are inactivated by heat, UV irradiation, and sometimes by treating with special chemicals (formalin and beta propiolactone) [152], for example, polio vaccines.

3. Recombinant viral proteins: By using bacteria, yeast, mammalian cell lines, insect, etc. desired viral proteins are manufactured, which are used as vaccine antigens [153], for example, vaccines for influenza viruses.

4. Subunit vaccines: Purified preparations are produced instead of whole inactivated vaccines [154]. The purified preparations containing main targets of protective immune responses were developed [150], for example, hepatitis B vaccines.

5. Virus-like particles: From structural proteins of virus, multimeric structure are assembled, which provide immune response against viruses [155,156], for example, hepatitis B vaccines.

Some antiviral vaccines have been developed successfully. However, in some cases, this is not possible due to many factors, such as [150,151,157]: (i) some viruses show wide genetic variations, (ii) some viruses integrate their genomes in the host, (iii) multiple mechanisms involve for evading host-immune detection and response, and (iv) ability for developing latency. In the present pandemic situation (COVID-19), some vaccines have been developed and approved on emergency basis [158]. However, more studies are required regarding safety and efficacy.

1.7 Immunotherapy and role of nutraceuticals in viral infection

The importance of immunotherapy in the management of viral infections is increasing day by day. Immunotherapy regulates the host’s adaptive (activated by exposure to pathogen) and innate immune responses against the viral infections [159]. Different viral infections, for example, COVID-19, are significantly controlled by immunotherapy, including T-cell-based therapies, vaccines, monoclonal antibodies (mAbs)-based therapies, etc. [160,161]. mAbs have been successfully employed, produced in the laboratory, and widely used for the treatment of various types of diseases [162–164]. They are safe, have high specificity, have capacity to target specific epitopes, and also have high potency. Use of vaccines is the most popular and cost-effective strategy and also one of the oldest therapies for viral infections. Chimeric antigen receptor T cells are also effective for immunotherapy in case of malignancies as well as viral infections [165]. Importance of nutraceuticals as immunomodulators is increasingly investigated to treat viral infections [166,167]. Nutraceuticals are usually food or food products having nutritional value and provide health and medical benefits and also can be used for the prevention and treatment of diseases. Nutraceuticals having specific health benefits can be called as potential nutraceuticals, for example, probiotic, prebiotic, antioxidants, dietary fibers, polyunsaturated fatty acids, etc. [166]. They are obtained from plant, animal, and microbial sources. Various types of nutraceuticals, their sources, and activities against viral infections are shown in Table 1.5.

Table 1.5

1.8 Challenges in the development of antiviral agents

Many antimicrobial agents are being developed on a regular basis. The rate of development of new antiviral agents is less as compared to emerging viruses. Despite the simplicity in the structures of viruses, there are so many challenges like antiviral drug resistance, mutations, etc. that limit the development of new molecules. Other issues include the cost of production of antiviral agents, preference of vaccination over treatment of viral infections with antiviral drugs, and the prolonged and time-consuming process of development of new antiviral agents (there may be a chance of occurrence of new variant due to mutation as observed in SARS-CoV-2 before the new drug is launched in the market) [173].

To overcome the above challenges in the development of effective antiviral agents, many strategies have been designed [174]. Attempts have been made to target host cell factors or the viruses (viral proteins/enzymes) [175,176], interference of the virus attachment with the host cells [177], inhibition of viral entry (fusion inhibitor) [177,178], inhibition of replication and transcription (polymerase inhibitors) [179,180] and inhibition of proteases [181,182] responsible for viral replication/transcription and maturation. Monoclonal antiboldies (mAbs) are also being developed as significant therapeutic agents against viral infections [162,163]. The antibody variable gene sequencing techniques and B-cell isolation in the evaluation of several agents against some viruses, for example, ZIKV, INFV, HIV, SARS-CoV-2, etc., have been identified [164,183].

1.9 Conclusion

With time, the number of diseases due to viruses is increasing. The genetic variation of viruses is wide and most of the viruses have a great tendency for mutation, which caused difficulty in the development of antiviral agents. The viruses are transmitted very fast by various means and lead to death of a large number of people within a very short period. Vaccines are being developed to control many such viral infections. Some antiviral agents have already been developed and successfully employed in the management of viral infections. Many more suitable antiviral agents are yet to be developed for effective control of different types of viral infections.

References

1. Crawford DH. Viruses: a very short introduction US: Oxford University Press; 2011;16.

2. Fields BN, Knipe DM, Howley P, Chanock RM, eds. Fields’ virology. 3rd ed. New York: Raven Press; 1995.

3. Pellett PE, Mitra S, Holland TC. Basics of virology. Handb Clin Neurol. 2014;123:45–66.

4. Koonin EV, Starokadomskyy P. Are viruses alive? The replicator paradigm sheds decisive light on an old but misguided question. Stud Hist Philos Biol Biomed Sci. 2016;59:125–134.

5. Mourya DT, Yadav PD, Ullas PT, et al. Emerging/re-emerging viral diseases & new viruses on the Indian horizon. Indian J Med Res. 2019;149(4):447–467.

6. Herrington CS, Coates PJ, Duprex WP. Viruses and disease: emerging concepts for prevention, diagnosis and treatment. J Pathol. 2015;235(2):149–152.

7. Gelderblom HR. Structure and classification of viruses. In: Baron S, ed. Medical microbiology. 4th ed. Galveston: University of Texas Medical Branch at Galveston; 1996.

8. Louten J. Virus structure and classification. Essential human virology 2016;19–29.

9. Du L, He Y, Zhou Y, Liu S, Zheng BJ, Jiang S. The spike protein of SARS-CoV–a target for vaccine and therapeutic development. Nat Rev Microbiol. 2009;7(3):226–236.

10. Chappell JD, Dermody TS. Biology of viruses and viral diseases. Mandell, Douglas, Bennett’s Princ Pract Infect Dis 2015;1681–1693 e4.

11. Villar E. Cell response to viral infection: search for new therapeutric targets. Virus Res. 2015;209:1–3.

12. Nagy PD, Richardson CD. Viral replication-in search of the perfect host. Curr Opin Virol. 2012;2(6):663–668.

13. Kasman LM, Porter LD. Bacteriophages. StatPearls [Internet] Treasure Island, FL: StatPearls Publishing; 2022.

14. Cohen FS. How viruses invade cells. Biophys J. 2016;110(5):1028–1032.

15. Dolgin E. The secret social lives of viruses. Nature. 2019;570(7761):290–292.

16. Cossart P, Helenius A. Endocytosis of viruses and bacteria. Cold Spring Harb Perspect Biol. 2014;6(8):a016972.

17. Cann AJ. Replication of viruses. Encycl Virol 2008;406–412.

18. Louten J. Virus replication. Essent Hum Virol 2016;49–70.

19. Payne S. Introduction to RNA viruses. Viruses 2017;97–105.

20. Venkataraman S, Prasad BVLS, Selvarajan R. RNA dependent RNA polymerases: insights from structure, function and evolution. Viruses. 2018;10(2):76.

21. Rampersad S, Tennant P. Replication and expression strategies of viruses. Viruses 2018;55–82.

22. Prasad BV, Schmid MF. Principles of virus structural organization. Adv Exp Med Biol. 2012;726:17–47.

23. Lidmar J, Mirny L, Nelson DR. Virus shapes and buckling transitions in spherical shells. Phys Rev E. 1910;68(5 Pt 1):05.

24. Rheinemann L, Sundquist WI. Virus budding. Encycl Virol 2021;519–528.

25. Louten J. Virus transmission and epidemiology. Essent Hum Virol 2016;71–92.

26. Jayaweera M, Perera H, Gunawardana B, Manatunge J. Transmission of COVID-19 virus by droplets and aerosols: a critical review on the unresolved dichotomy. Env Res. 2020;188:109819.

27. Rodríguez-Lázaro D, Cook N, Ruggeri FM, et al. Virus hazards from food, water and other contaminated environments. FEMS Microbiol Rev. 2012;36(4):786–814.

28. Riad A, Hockova B. Vertical transmission. Br Dent J. 2020;229(2):71.

29. Tripathi S, Awasthi S, Singh SN, Kumar M. Vertical transmission of COVID-19. Indian J Pediatr. 2021;88(10):1058.

30. Martinez-Portilla RJ. Vertical transmission of coronavirus disease 2019. Am J Obstet Gynecol. 2021;224(3):328–329.

31. Lawrence RM, Lawrence RA. Breast milk and infection. Clin Perinatol. 2004;31(3):501–628.

32. Michie CA, Gilmour J. Breast feeding and the risks of viral transmission. Arch Dis Child. 2001;84(5):381–582.

33. Michie CA, Gilmour JW. Breastfeeding and viral transmission: risks, benefits and treatments. J Trop Pediatr. 2000;46(5):256–257.

34. Kutter JS, Spronken MI, Fraaij PL, Fouchier RA, Herfst