The Design and Development of Novel Drugs and Vaccines: Principles and Protocols

by Tarun Kumar Bhatt (Editor), Surendra Nimesh (Editor)

Overview

The Design and Development of Novel Drugs and Vaccines: Principles and Protocols presents both in silico methods and experimental protocols for vaccine and drug design and development, critically reviewing the most current research and emphasizing approaches and technologies that accelerate and lower the cost of product development. Sections review the technologies and approaches used to identify, characterize and establish a protein as a new drug and vaccine target, cover several molecular methods for in vitro studies of the desired target, and present various physiological parameters for in vivo studies. The book includes preclinical trials and research, along with information on FDA approval.

Product Details

ISBN-13:	9780128214718
Publisher:	Elsevier Science
Publication date:	01/22/2021
Pages:	308
Product dimensions:	6.00(w) x 9.00(h) x (d)

About the Author

Tarun Kumar Bhatt is an Assistant Professor in the Department of Biotechnology, at the Central University of Rajasthan, India. He received his PhD from the International Centre for Genetic Engineering and Biotechnology, New Delhi and gained post-doctoral experience at the Scripps Research Institute in San Diego, California. He has published over 25 articles and has extensive experience researching drug and vaccine development.

Surendra Nimesh, UGC Assistant Professor at Central University of Rajasthan, Rajasthan, India. Surendra received his M.S. in Biomedical Science from the Dr. B.R. Ambedkar Center for Biomedical Research (ACBR), University of Delhi. He completed his PhD. In Nanotechnology at the Institute of Genomics and Integrative Biology (CSIR), Delhi. After completing his postdoctoral studies at the Ecole Polyetchnique of Montreal, Surendra joined the Clinical Research Institute of Montreal (IRCM), Canada as Postdoctoral Fellow. After completing his commitment at IRCM, he joined McGill University for short time. He also worked as NSERC visiting fellow at Health Canada, Canada. His research interests include nanoparticles-mediated gene, siRNA and drug delivery.

Table of Contents

Contributors xv

Preface xvii

Part A Computational drug design

1 Introduction of structural bioinformatics with respect to drug discovery Hemant Arya Mohane Selvaraj Coumar Tarun Kumar Bhatt

1 Overview 3

1.1 Drug discovery 3

1.2 Structural bioinformatics (SB) 5

Frequently asked questions (FAQs) 7

References 7

2 Target identification and validation Hemant Arya Mohane Selvaraj Coumar

1 Overview 11

2 Steps involved in in silico target identification 13

Frequently asked questions (FAQs) 19

References 19

3 Retrieval of compounds Hemant Arya Mohane Selvaraj Coumar Tarun Kumar Bhatt

1 Overview 21

1.1 Natural products 21

1.2 Literature/chemical libraries 21

1.3 Computational chemistry 22

1.4 Steps involved in lead identification 23

Frequently asked questions (FAQs) 28

References 28

4 Lead identification and optimization Hemant Arya Mohane Selvaraj Coumar

1 Overview 31

2 Lead identification 31

2.1 Virtual screening 31

3 Lead optimization 32

3.1 Computer-aided drug design (CADD) 32

3.2 Molecular modeling 33

3.3 Structure-based drug design (SBDD) 33

3.4 Ligand-based drug design (LBDD) 34

4 Modeller installation 36

4.1 Steps involved in homology modeling using Modeller software 36

4.2 Steps involved in homology modeling using I-TASSER online tool 40

5 WHAT IF 41

6 Steps involved in molecular docking 41

7 AutoDock tool installation 42

7.1 Steps involved in molecular docking using AutoDock tool 42

8 Pharmacophore modeling using BRUSELAS 57

8.1 Steps involved in pharmacophore modeling 58

Frequently asked questions (FAQs) 61

References 61

5 Molecular dynamics simulations Hemant Arya Tarun Kumar Bhatt

1 Overview 65

2 Gromacs installation 66

3 Steps involved in molecular dynamics simulation of protein using Gromacs software 67

4 Molecular dynamics simulation result analysis 76

Frequently asked questions (FAQs) 80

References 80

Part B Computational vaccine design

6 An overview of vaccine design Hemant Arya Tarun Kumar Bhatt

1 Overview 85

2 Key features of a potential vaccine 85

3 Components of an ideal vaccine 86

4 Role of bioinformatics in vaccine design 87

5 An ideal vaccine design process 87

5.1 Potential vaccine target identification 88

5.2 B and T cell epitope prediction 88

5.3 Linker and adjuvant selection 88

5.4 Construct design and antigenicity/allergenicity prediction 88

5.5 Structure prediction, protein-protein interactions and stability analysis 89

5.6 Construct synthesis and cloning 89

5.7 Expression, purification of the construct and biological assay 89

Frequently asked questions (FAQs) 89

Acknowledgments 90

References 90

7 Key steps in the selection of vaccine targets Hemant Arya

1 Overview 93

2 Vaxigen 94

Frequently asked questions (FAQs) 94

Acknowledgments 95

References 95

8 Epitope prediction and selection of linkers and adjuvant Hemant Arya

1 Overview 97

1.1 Epitope 97

1.2 B-cell epitope prediction 98

1.3 T-cell epitope prediction 98

1.4 Linkers 99

1.5 Adjuvant 99

1.6 B-cell epitope prediction 100

1.7 Steps involved in T-cell epitope prediction using IEDB 102

Frequently asked questions (FAQs) 105

Acknowledgments 106

References 106

9 Design of vaccine constructs Hemant Arya Tarun Kumar Bhatt

1 Overview 109

1.1 Vaccine construct 109

1.2 Antigenicity, allergenicity, toxicity, solubility and stability prediction 110

1.3 Protocols 111

Frequently asked questions (FAQs) 117

Acknowledgments 118

References 118

10 In silico validation through protein-protein docking Hemant Arya

1 Overview 121

1.1 Protein-protein interaction 121

1.2 Molecular dynamics of the protein-protein complex 122

1.3 Steps involved in protein-protein interaction (PPI) using the HADDOCK server 122

Frequently asked questions (FAQs) 130

Acknowledgments 131

References 131

Part C In vitro study

11 Molecular cloning Praveen Rai Hemant Arya

1 Overview 135

1.1 Molecular cloning 135

1.2 Component required for cloning 135

1.3 Types of cloning 136

2 PCR (polymerase chain reaction) 136

3 Type of molecular cloning 139

3.1 Restriction enzyme cloning 139

3.2 Vectors preparation 140

3.3 TA cloning 144

4 Transformation 146

4.1 Bacterial competent cell preparation and transformation 146

4.2 Transformation 147

4.3 Yeast cell preparation and transformation 147

4.4 Transfection 150

4.5 Insect cell transfection 158

Frequently asked questions (FAQs) 160

References 161

Further reading 162

12 Protein expression Praveen Rai Diwakar Kumar

1 Protein expression 165

1.1 Key features of the Prokaryotic vs. Eukaryotic translation machinery 165

1.2 E. coli-based protein expression 165

1.3 Yeast expression system 175

1.4 Mammalian cell line expression 177

Frequently asked questions (FAQs) 179

References 180

13 Protein purification and desalting Praveen Rai Hemant Arya Diwakar Kumar

1 Overview 181

1.1 Protein purification 181

2 Types of protein purification 183

2.1 Affinity chromatography (AC) 183

2.2 Ion exchange chromatography 190

2.3 Gel filtration chromatography 192

2.4 Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) 194

2.5 Western blot 197

Frequently asked questions (FAQs) 199

References 200

14 Biological assay Praveen Rai Sujeet Singh Surendra Nimesh

1 Overview 203

1.1 Biological assay 203

Frequently asked questions (FAQs) 209

References 210

15 Biophysical methods Praveen Rai Sujeet Singh Surendra Nimesh

1 Biophysical assay/methods 211

1.1 Crystallography 211

1.2 Surface plasmon resonance (SPR) 214

1.3 Circular dichroism (CD) 218

Frequently asked questions (FAQs) 220

References 220

Part D In vivo study

16 Outline of animal study for lead/vaccine testing Aparna Satapathy Surendra Nimesh

Overview 225

1 Selection of animal model 226

1.1 HIV 226

1.2 Zika virus 226

1.3 Chikungunya virus 226

1.4 Tuberculosis 226

1.5 Malaria 226

1.6 Leishmaniasis 227

2 Ethical guidelines 227

3 Animal profile 228

4 Standard dose selection 228

5 Mode of administration 230

6 Experimental group 230

Frequently asked questions (FAQs) 231

References 231

17 Evaluation of immunogenicity of vaccine candidates Aparna Satapathy Tarun Kumar Bhatt

1 Overview 233

1.1 ELISA assays for quantification of antibody concentration 233

1.2 Determination of T-cell immune response from mice 234

1.3 Detection of cytokine profiling from mice 235

1.4 Parasite inhibition assay for Plasmodium falciparum 236

Frequently asked questions (FAQs) 236

References 237

18 In-vitro evaluation of lead molecule Aparna Satapathy Tarun Kumar Bhatt

1 Overview 239

1.1 Microscopy based parasite count 239

1.2 PCR based parasite count 242

1.3 Flow cytometry method for parasite count 243

Frequently asked questions (FAQs) 244

References 245

19 Medical physiological parameter for lead/vaccine testing Aparna Satapathy Surendra Nimesh

1 Overview 247

1.1 Biochemical indices 248

1.2 Serum parameters 251

1.3 Hematological indices 253

1.4 Antioxidant parameters 254

Frequently asked questions (FAQs) 256

References 258

Part E Clinical trials and FDA approval

20 Brief introduction of clinical research and trials Hemant Arya Mohane Selvaraj Coumar Tarun Kumar Bhatt

1 Overview 263

Frequently asked questions (FAQs) 265

References 265

21 An overview of IND, NDA, approval agencies and FDA post-marketing surveillance Hemant Arya Surendra Nimesh

1 Overview 267

2 Investigational new drug (IND) 268

3 New drug application (IMDA) 269

4 FDA post-marketing safety monitoring 271

Frequently asked questions (FAQs) 272

References 272

22 Introduction of intellectual property rights Hemant Arya Tarun Kumar Bhatt

1 Overview 275

1.1 Copyrights 275

1.2 Trademarks and service mark 276

1.3 Trade secrets 276

1.4 Geographical indication (Gl) 277

1.5 Traditional knowledge 277

1.6 Patents 278

2 How to fill the patent application in the US and India? 278

2.1 Patent application filing in India 278

2.2 Patent application filing in the US 279

Frequently asked questions (FAQs) 280

References 281

Index 283

What People are Saying About This

From the Publisher

A comprehensive accounting of drug and vaccine development methods and protocols that covers both in silico and experimental techniques

Editorial Reviews

Reviewer: Patrick J Scoble, PharmD (PJS Pharma Consulting LLC)
Description: This book on the components of drug development for novel agents or vaccines is an amalgamation of multiple foci of drug development.
Purpose: The purpose is to provide a solid foundation of drug design, especially in the scope of vaccine development. Providing a ready reference for drug/vaccine developers is a worthy objective. This book provides a detailed, methodical approach from concept through design to the end result with the FDA review process.
Audience: The audience includes students, residents, research fellows, and early researchers. The book seems to be geared toward infectious diseases researchers who specialize in vaccine development.
Features: The book covers drug design in great detail, particularly the scope of vaccine development. The best aspects of the book include the detail with which the drug design portion of drug development is described. Many early researchers would benefit from reading this part of the book. A shortcoming of the book is the amount of time allotted to the section on clinical trials and FDA approval.
Assessment: I have read other books on clinical research, but none with the level of detail and particular focus on drug design (the computational drug design sections) that this one has. This book is very detailed-oriented from that standpoint, and it can certainly serve as a useful tool for those developing vaccines

Doody's Review Service

"I have read other books on clinical research, but none with the level of detail and particular focus on drug design (the computational drug design sections) that this one has. This book is very detailed-oriented from that standpoint, and it can certainly serve as a useful tool for those developing vaccines." —© Doody’s Review Service, 2021, Patrick J Scoble, PharmD(PJS Pharma Consulting LLC), reviewer, expert opinion

From the Publisher