A Guide to Virology for Engineers and Applied Scientists

Megan M. Reynolds, BSChE, MS, MBA, is a freelance medical writer and editor with a focus on infectious diseases. She holds degrees in chemical engineering, international business, and medicine, and has more than 12 years’ experience in the pharmaceutical industry in a variety of capacities. Louis Theodore, MChE, EngScD, is a retired professor of chemical engineering with over 50 years’ education experience. He has authored numerous publications and has served as section editor to the last four editions of Perry’s Chemical Engineer’s Handbook. Dr. Theodore currently works as an environmental engineering consultant.

Preface xvii

About the Authors xix

Part I Introduction to Viruses 1

1 Overview of Molecular Biology 3
Contributing Author: Sarah Forster

1.1 Cell Basics 4

1.1.1 Cytoplasm 5

1.1.2 Ribosomes 5

1.1.3 Nucleus 6

1.2 Cell Replication 6

1.2.1 Nucleic Acids 6

1.2.2 DNA Replication 7

1.2.3 RNA Structure and Role 9

1.2.4 Protein Synthesis 9

1.3 Cellular Transport 11

1.3.1 Plasma Membrane 11

1.3.2 Cell Signaling 11

1.4 Immune Defense 12

1.4.1 Innate Immunity 12

1.4.2 Adaptive Immunity 13

1.4.2.1 Humoral Immunity 13

1.4.2.2 Cellular Immunity 14

1.5 Applications 14

1.6 Chapter Summary 16

1.7 Problems 16

References 16

2 Basics of Virology 19

2.1 Viral Basics and Terminology 19

2.2 Viral Life Cycle 21

2.2.1 Attachment (Connection) 21

2.2.2 Penetration (Entry) 22

2.2.3 Uncoating 22

2.2.4 Replication 23

2.2.5 Assembly 23

2.2.6 Maturation and Release 23

2.3 Virus Structure and Classification 24

2.3.1 DNA Viruses 25

2.3.2 RNA Viruses 25

2.3.3 Reverse Transcription Viruses (Retroviruses) 27

2.4 Viruses in Context of the Tree of Life 27

2.5 Viral Genetics 28

2.5.1 Antigenic Shift 28

2.5.2 Antigenic Drift 29

2.5.3 Phenotypic Mixing 29

2.5.4 Complementation 29

2.6 Applications 29

2.7 Chapter Summary 31

2.8 Problems 31

References 32

3 Pandemics, Epidemics, and Outbreaks 33

3.1 Human Viral Diseases 34

3.2 Ebola and Marburg Viruses 35

3.2.1 Symptoms 36

3.2.2 Diagnosis 37

3.2.3 Prevention and Treatment 37

3.3 Human Immunodeficiency Disease (HIV) 38

3.3.1 HIV Symptoms 39

3.3.1.1 Stage 1: Acute Infection 39

3.3.1.2 Stage 2: Chronic HIV Infection (Latent Phase) 39

3.3.1.3 Stage 3: Acquired Immunodeficiency Syndrome (AIDS) 39

3.3.2 Diagnosis 40

3.3.3 HIV Prevention and Treatment 40

3.4 Influenza 41

3.4.1 Influenza Symptoms 41

3.4.2 Influenza Diagnosis 42

3.4.3 Influenza Prevention and Treatment 42

3.4.4 Influenza Pandemics 43

3.5 Coronaviruses 44

3.5.1 Symptoms 45

3.5.1.1 Typical Acute Symptoms 45

3.5.1.2 Post-COVID Conditions 46

3.5.1.3 COVID-19 Multiorgan System Effects (MIS) 46

3.5.2 COVID-19 Diagnosis 47

3.5.3 COVID-19 Prevention and treatment 48

3.6 Current and Emerging Viral Threats 48

3.7 Applications 51

3.8 Chapter Summary 52

3.9 Problems 53

References 53

4 Virus Prevention, Diagnosis, and Treatment 57

4.1 Vaccination Successes and Challenges 58

4.2 Current Vaccine Technology 59

4.2.1 Live-attenuated vaccines 60

4.2.2 Inactivated vaccines 61

4.2.3 Recombinant Subunit Vaccines 61

4.2.4 Viral Vector Vaccines 62

4.2.5 Messenger RNA (mRNA) Vaccines 62

4.3 U.S.-Approved Vaccines and Requirements 63

4.3.1 Commercially Available Viral Vaccines 63

4.3.2 Vaccination Requirements 63

4.4 Viral Testing and Diagnosis 64

4.4.1 Viral Testing 65

4.4.2 Antibody Testing 66

4.5 Antiviral Treatment Options 66

4.5.1 HIV 67

4.5.1.1 Nucleoside Reverse Transcriptase Inhibitors (NRTIs) 67

4.5.1.2 Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs) 67

4.5.1.3 Protease Inhibitors (PIs) 67

4.5.1.4 Fusion Inhibitors (FIs) 67

4.5.1.5 Integrase Strand Transfer Inhibitors (INSTIs) 67

4.5.1.6 CCR5 Antagonists 67

4.5.1.7 Attachment Inhibitors 68

4.5.1.8 Post-Attachment Inhibitors 68

4.5.1.9 Pharmacokinetic Enhancers 68

4.5.2 Influenza 68

4.5.3 Hepatitis C virus (HCV) 68

4.5.4 Other Treatment Options 69

4.6 Applications 70

4.7 Chapter Summary 71

4.8 Problems 72

References 72

5 Safety Protocols and Personal Protection Equipment 75
Contributing Author: Emma Parente

5.1 Regulations and Oversight of Safety Protocols 76

5.2 Protective and Safety Systems 76

5.2.1 Personal Protective Devices and Practices 76

5.2.2 Antimicrobial Suppression And Eradication 77

5.3 Disinfection Categories and Procedures 78

5.4 Occupational Health and Safety Administration Hazmat Regulations 79

5.4.1 HAZMAT Level A Protection 80

5.4.2 HAZMAT Level B Protection 81

5.4.3 Level C Protection 82

5.4.4 Level D Protection 83

5.5 Bio Level Safety and Security 83

5.6 COVID-Related Safety Precautions 84

5.6.1 Personal Protective Equipment 84

5.6.2 Transmission Control 85

5.7 Applications 85

5.8 Summary 87

5.9 Problems 87

References 88

6 Epidemiology and Virus Transmission 91

6.1 Overview of Epidemiology 92

6.2 Government Agencies’ Contributions to Public Health 94

6.2.1 The Role of the Centers for Disease Control and Prevention (CDC) 94

6.2.2 The World Health Organization (WHO): Successes and Challenges 95

6.3 Epidemiologic Study Design 96

6.3.1 Outbreak Case Example 98

6.3.2 Clinical Trials 99

6.4 Virus Transmission 100

6.4.1 Modes of Transmission 101

6.5 Applications 102

6.6 Chapter Summary 104

6.7 Problems 105

References 105

Part II Practical and Technical Considerations 109

7 Engineering Principles and Fundamentals 111
Contributing Author: Vishal Bhatty

7.1 History of Engineering 112

7.2 Problem Solving: The Engineering Approach 113

7.2.1 Problem-Solving Methodology 114

7.2.2 Engineering and Scientific Sources 115

7.3 Units and Conversion Constants 115

7.3.1 The Metric System 115

7.3.2 The SI System 117

7.4 Dimensional Analysis 117

7.5 Process Variables 119

7.6 The Conservation Laws 121

7.7 Thermodynamics and Kinetics 125

7.8 Applications 126

7.9 Chapter Summary 130

7.10 Problems 130

References 131

8 Legal and Regulatory Considerations 133

8.1 The Regulatory System 134

8.1.1 Laws, Regulations, Plans and policy: The Differences 135

8.1.2 Policies and Plans 137

8.2 The Role of Individual States 138

8.3 Key Government Agencies 140

8.3.1 Environmental Protection Agency (EPA) 140

8.3.2 Centers for Disease Control and Prevention (CDC) 141

8.3.3 Food and Drug Administration (FDA) 141

8.3.4 Occupational Health and Safety Administration (OSHA) 141

8.3.5 Legal Considerations during a Public Health Crisis 142

8.4 Public Health Emergency Declarations 143

8.5 Key Environmental Acts 145

8.6 The Clean Air Act 145

8.7 Regulation of Toxic Substances 147

8.7.1 Toxic Water Pollutants: Control and Classification 150

8.7.2 Drinking Water 150

8.7.3 Surface Water Treatment Rules (SWTR) 151

8.8 Regulations Governing Infectious Diseases 153

8.8.1 Vaccination Laws 155

8.8.2 State Healthcare Worker and Patient Vaccination Laws 155

8.8.3 State-Mandated Childhood Vaccinations 155

8.9 Applications 155

8.10 Chapter Summary 159

8.11 Problems 159

References 160

9 Emergency Planning and Response 163

9.1 The Importance of Emergency Planning and Response 164

9.2 Planning for Emergencies 166

9.2.1 Preparedness Training 166

9.3 Plan Implementation 167

9.3.1 Notification of Public and Regulatory Officials 168

9.4 EP&R for Epidemics and Pandemics 169

9.4.1 Federal Public Health and Medical Emergency Preparedness 170

9.4.2 Emergency Operations Center 170

9.4.3 Disease Containment 172

9.4.4 Public Notification of Pandemic Quarantines and Lockdowns 173

9.4.5 The National Strategy for Pandemic Influenza (NSPI) 173

9.5 EP&R for Industrial Accidents 174

9.5.1 Emergency Planning and Community Right-to-Know Act (epcra) 175

9.5.2 The Planning Committee 177

9.6 EP&R for Natural Disasters 179

9.7 Current and Future Trends 181

9.8 Applications 181

9.9 Chapter Summary 184

9.10 Problems 184

References 185

10 Ethical Considerations within Virology 189
Contributing Author: Paul DiGaetano, Jr.

10.1 Core Ethics Principles 190

10.2 Important Tenets of Ethical Research 191

10.2.1 Conducting Research During a Health Crisis 192

10.2.2 Scientific Cooperation During a Health Crisis 192

10.2.3 Fair and Ethical Study Design and Implementation 193

10.3 Ethical Dilemmas in Public Health 193

10.3.1 Public Health Surveillance 193

10.3.2 Ethical Evaluation of Nonpharmaceutical Interventions 195

10.3.3 Ethical Consideration Involving Restrictions of Movement 197

10.4 Ethical Considerations Regarding Medical Interventions 199

10.4.1 Emergency Use Of Medical Interventions 200

10.5 Applications 201

10.6 Chapter Summary 202

10.7 Problems 203

References 203

11 Health and Hazard Risk Assessment 205

11.1 Introduction to Risk Assessment 207

11.2 The Health Risk Assessment Process 209

11.3 Dose–Response Assessment 211

11.4 The Hazard Risk Assessment Process 213

11.5 Hazard Risk Versus Health Risk 214

11.5.1 Health Risk Assessment (HRA) Example 215

11.5.2 Hazard Risk Assessment (HRZA) Example 215

11.6 COVID-19 Pandemic Hazard Risk 216

11.7 The Uncertainty Factor 217

11.8 Applications 218

11.9 Chapter Summary 220

11.10 Problems 220

References 221

Part III Engineering Considerations 223

12 Introduction to Mathematical Methods 225
Contributing Author: Julian Theodore

12.1 Differentiation 226

12.2 Integration 228

12.2.1 The Trapezoidal Rule 228

12.2.2 Simpson’s Rule 229

12.3 Simultaneous Linear Algebraic Equations 230

12.3.1 Gauss–Jordan Reduction 231

12.3.2 Gauss Elimination 232

12.3.3 Gauss–Seidel Approach 232

12.4 Nonlinear Algebraic Equations 233

12.5 Ordinary Differential Equations 234

12.6 Partial Differential Equations 237

12.7 Applications 237

12.8 Chapter Summary 240

12.9 Problems 240

References 241

13 Probability and Statistical Principles 243

13.1 Probability Definitions and Interpretations 244

13.2 Introduction to Probability Distributions 246

13.3 Discrete Probability Distributions 247

13.3.1 The Binomial Distribution 248

13.3.2 Multinomial Distribution 248

13.3.3 Hypergeometric Distribution 249

13.3.4 Poisson Distribution 250

13.4 Continuous Probability Distributions 250

13.4.1 Measures of Central Tendency and Scatter 251

13.4.2 The Normal Distribution 252

13.4.3 The Lognormal Distribution 256

13.4.4 The Exponential Distribution 257

13.4.5 The Weibull Distribution 258

13.5 Contemporary Statistics 259

13.5.1 Confidence Intervals for Means 260

13.5.2 Confidence Intervals for Proportions 260

13.5.3 Hypothesis Testing 261

13.5.4 Hypothesis Test for Means and Proportions 261

13.5.5 The F Distribution 262

13.5.6 Analysis of Variance (ANOVA) 262

13.5.7 Nonparametric Tests 264

13.6 Applications 264

13.7 Chapter Summary 268

13.8 Problems 268

References 269

14 Linear Regression 271

14.1 Rectangular Coordinates 272

14.2 Logarithmic Coordinates 273

14.3 Methods of Plotting Data 275

14.4 Scatter Diagrams 275

14.5 Curve Fitting 278

14.6 Method of Least Squares 280

14.7 Applications 284

14.8 Chapter Summary 287

14.9 Problems 288

References 288

15 Ventilation 289

15.1 Introduction to Industrial Ventilation Systems 290

15.2 Components of Ventilation Systems 291

15.3 Fans, Valves and Fittings, and Ductwork 293

15.3.1 Fans 293

15.3.2 Valves and Fittings 295

15.4 Selecting Ventilation Systems 296

15.5 Key Process Equations 298

15.5.1 Regarding Friction Losses 299

15.6 Ventilation Models 300

15.7 Model Limitations 302

15.8 Infection Control Implications 303

15.9 Applications 305

15.10 Chapter Summary 309

15.11 Problems 310

References 310

16 Pandemic Health Data Modeling 313

16.1 COVID-19: A Rude Awakening 315

16.2 Earlier Work 316

16.3 Planning for Pandemics 318

16.4 Generating Mathematical Models 319

16.5 Pandemic Health Data Models 324

16.6 In Review 329

16.7 Applications 331

16.8 Chapter Summary 338

16.9 Problems 338

References 339

17 Optimization Procedures 341

17.1 The History of Optimization 342

17.2 The Scope of Optimization 344

17.3 Conventional Optimization Procedures 346

17.4 Analytical Fomulation of the Optimum 347

17.5 Contemporary Optimization: Concepts in Linear Programming 350

17.6 Applied Concepts in Linear Programming 351

17.7 Applications 355

17.8 Chapter Summary 357

17.9 Problems 358

References 359

Index 361