Antiviral Therapeutics - Technologies, Markets and Companies

Feb 01, 2012, 05:25 ET from Reportlinker

NEW YORK, Feb. 1, 2012 /PRNewswire/ -- announces that a new market research report is available in its catalogue:

Antiviral Therapeutics - Technologies, markets and companies

This report reviews the current state-of-art of antiviral approaches including vaccines, pharmaceuticals and innovative technologies for delivery of therapeutics. The introduction starts with a practical classification of viral diseases according to their commercial importance. Various antiviral approaches are described including pharmaceuticals and molecular biological therapies such as gene therapy and RNA interference (RNAi) as well as vaccines for virus infections. Expert opinion is given about the current problems and needs in antiviral therapy. SWOT (strengths, weaknesses, opportunities and threats) analysis of antiviral approaches is presented against the background of concept of an ideal antiviral agent.

A novel feature of this report is the use of nanotechnology in virology and its potential for antiviral therapeutics. Interaction of nanoparticles with viruses are described. NanoViricides are polymeric micelles, which act as nanomedicines to destroy viruses. Various methods for local as well as systemic delivery of antiviral agents and vaccines are described. Nanobiotechnology plays an important role in improving delivery of antivirals. Advantages and limitations of delivery of gene-based, antisense and RNAi antiviral therapeutics are discussed.

Anti-influenza measures applicable to human as well as avian forms are described including the recent epidemic of swine flu. Resistance can develop against neuraminidase inhibitors although it is less than that with adamantanes. Considering these problems, there is need for a more effective agent. Investigations into alternative anti-influenza target will probably expand in the coming years. These include the development of mechanisms to inhibit fusion between the virus envelope and the cell membrane.

After a discussion of current therapies of AIDS/HIV and their limitations, new strategies in development of antiviral agents are described. Drug resistance and toxicities are emerging as major treatment challenges. Based on a review of technologies and drugs in development, it can be stated that there are good prospects are of finding a cure for HIV/AIDS in the next decade.

Hepatitis viruses are described with focus on hepatitis C virus (HCV) and hepatitis B virus (HBV). Despite the presence of numerous drug candidates in the anti-HCV pipeline, and the commitment of major R&D resources by many pharmaceutical companies, it might still take several years for any new anti-HCV drugs to reach the market. Although many companies are focusing their efforts on developing viral inhibitors, cellular targets in the host are beginning to emerge as attractive possibilities because they might enable the development of broad-spectrum antiviral drugs with less chance for developing viral resistance.

Various commercially important viruses include herpes simplex (HSV) and human papilloma virus (HPV). There a number of treatments but HSV is not destroyed completely and remains dormant and activates from time to time to cause various clinical manifestations. There is discussion about the role of HPV in cervical cancer and vaccines available now seem to be adequate in preventing HSV-induced cervical cancer. There is no effective vaccine for respiratory syncytial virus (RSV) although monoclonal antibody (MAb) treatment is useful for prophylaxis and reducing the clinical manifestations. There is a need for an agent to eliminate this virus.

Various viruses that either occur in epidemics or in tropics and some naturally emerging infectious diseases are described, e.g. viral hemorrhagic fevers such as dengue and West Nile virus infection. These are a constant threat and impossible to anticipate. Some of these lack antiviral agents or vaccines for prevention. Although these include some of the most serious viral disorders, the development of antiviral agents for these is not commercially attractive. Current research and approaches to these virus infections are discussed.

Markets for antivirals are considered according to viruses and diseases caused by them and also according to management approaches: antiviral drugs, vaccines, MAbs and innovative approaches that include immunological and use of other technologies such as gene therapy, antisense, RNAi and nanobiotechnology. Antiviral markets are estimated starting with 2010 with projections up to the year 2020.

Profiles of 178 companies that are involved in developing various technologies and products are profiled and with 161 collaborations. These include major pharmaceutical companies (13), those developing antiviral therapeutics (107) as well as viral vaccine companies (58). The report is supplemented with 49 tables, 11 figures and 450 references from the literature.

TABLE OF CONTENTS 0. Executive Summary 17

1. Introduction to Virology 19

Introduction 19

Virus databases 19

A practical classification of viruses 19

Pathomechanism of viral diseases relevant to therapy 20

Intrinsic host defense against retroviruses 21

Life cycle of virus as basis for antiviral approaches 22

Genetic switch in virus infections 22

Emerging viruses 23

Viral-induced cancer 23

Prophylaxis versus therapy 24

Economic impact of viral diseases 25

Historical landmarks in the development of antiviral therapies 25

2. Antiviral Approaches 27

Classification 27

Antiviral drug discovery and development 27

Viral versus cellular targets for antiviral therapy 27

Antivirals based on double-stranded RNA activated caspase oligomerizer 29

Antimicrobial peptides 29

Immunological approaches 29

Basics of immune regulation in relation to viruses 29

Effect of viruses on the immune system 30

Latent viral infections and the immune system 30

Immunomodulating agents 31

Amplification of innate immunity 31

Blocking the effects of thromboxane A2 on thromboxane receptor 31

Enhancers of immune system 32

Promoting immune-mediated clearance of a chronic viral infections 32

Immunoglobulins 32

Bovine lactoferrin 33

Quercetin 33

Monoclonal antibodies 34

Bavituximab 34

Treatment of viral infection with radiolabeled MAbs 35

Limitations of MAbs and measures to overcome these 35

Interferon-based approaches 35

Novel antiviral approaches 36

Squalamine 36

Synthetic modified hypericin compounds 36

Targeting Toll-like receptors 36

Potential and drawbacks of TLR-ligands in viral diseases 37

Inhibition of viral transport from cytoplasm into the cell nucleus 38

Nitric Oxide based antiviral therapeutics 38

Gene therapy for viral infections 38

Antisense approaches to viral infections 39

Antisense oligonucleotides 39

Limitations of antisense oligonucleotides as antivirals 40

NEUGENE antisense 40

RNAi 40

RNAi screens of viral genomes 41

RNAi for treatment of viral infections 41

Promise and pitfalls of RNAi gene therapy 42

Management of rapidly evolving pathogens 42

Personalized medicine and viral diseases 42

An integrated approach to viral diseases 43

Current problems and needs in antiviral therapy 43

3. Vaccines for Virus Infections 45

Introduction 45

Types of vaccines 46

Live attenuated virus vaccines 46

DNA vaccines 46

Nanotechnology-based vaccines 47

Recombinant viral vaccines 48

Synthetic peptides as vaccines 48

Virosomes 49

Vaccines based on reverse genetics 49

Virus-like particles 49

Routine vaccination in children against viral infections 50

Personalized vaccines 50

Limitations of vaccines 50

Neurological complications of vaccination 51

Expert opinion on antiviral vaccines 51

4. Role of Nanotechnology in Developing Antiviral Agents 53

Introduction 53

Study of interaction of nanoparticles with viruses 53

Nanoparticle antiviral agents 54

Silver nanoparticles 54

Fullerenes 54

Nanoviricides 55

Role of micelles in nanopharmaceuticals 55

Some physicochemical characteristics common to polymeric micelles 55

Structure and function of nanoviricides 56

Mechanism of action of NanoViricides 56

Advantages of NanoViricides 57

5. Delivery of Antivirals 59

Introduction 59

Methods of delivery of antiviral agents 59

Local application of antivirals 59

Systemic delivery of of protein-polymer antiviral drugs 60

Controlled delivery of antivirals 60

Targeted delivery of antivirals 60

Delivery of antivirals to the brain across the blood-brain barrier 61

Antiviral vaccine delivery systems 61

Minicell vaccine delivery 61

Transnasal delivery of vaccines by Newcastle disease virus as vector 61

Transdermal delivery of vaccines 62

CELLECTRA® electroporation device 62

Intramuscular electroporation for delivery of DNA vaccine 62

HIV/AIDS vaccination by transdermal application 62

Transdermal vaccines for influenza 63

Use of nanotechnology for improving delivery of antivirals 63

Macrophage-based nanoformulated antiretroviral therapy 64

Improvement of antiviral vaccine delivery by nanotechnology 65

Bacterial spores for delivery of vaccines 65

Liposomal antiviral vaccine preparations 65

Nanoparticles for DNA vaccines 65

Chitosan-derived nanoparticles for vaccine delivery 66

Use gold nanorods for delivery of RNA immune activator molecules 66

Proteosomes™ as vaccine delivery vehicles 66

Polymeric micellae for delivery of DNA vaccine 66

"Smart" nanoparticles for delivery of vaccines 67

Nanospheres for controlled release of viral antigens 67

Nanocoating for local viricidal effect 67

Delivery of gene-based antiviral drugs 68

Limitations of delivery of gene, RNAi and antisense therapies 68

Systemic delivery of NanoViricides 68

Concluding remarks on delivery of antiviral agents 69

6. Competitive Assessment of Antiviral Approaches 71

Introduction 71

An ideal antiviral agent 71

SWOT analysis 71

Concluding remarks 74

7. Influenza Viruses 75

Introduction 75

Clincal features of influenza 75

Colds due to rhinovirus 75

Effects of influenza on the respiratory system 76

Effect of avian influenza on the nervous system 76

Epidemiology 76

Supermap of avian influenza 76

Influenza A 77

Avian influenza affecting humans 77

Human influenza versus avian influenza 78

H1N1 influenza 79

Immune system and influenza 80

Immune Epitope Database and Analysis Resources 80

Anti-influenza approaches 81

Pharmaceuticals 81

Neuraminidase inhibitors 81

Mechanism of action 81

Tamiflu 82

Zanamivir 82

CS-8958 82

Peramivir 83

Resistance to neuraminidase inhibitors 83

Adverse effects of neuraminidase inhibitors 84

Other drugs for influenza 85

Adamantanes 85

Probenecid 85

Current recommendations for the use of antiviral agents for influenza 85

Vaccines 86

Seasonal influenza vaccines 86

Live attenuated influenza vaccine vs. inactivated vaccine 86

Vaccines for H1N1 influenza 87

Current status of influenza vaccines 88

Current recommendations for influenza vaccination 88

Current status of vaccine preparedness against seasonal influenza 88

Current status of vaccine preparedness against H5N1 89

Limitations, needs and challenges of influenza vaccines 89

Limitations of current influenza vaccines 89

Needs of influenza vaccines 90

Problems with demand and supply of influenza vaccines 91

Problems with access to virus samples 91

FluVac project for development of pandemic influenza vaccine 91

Influenza vaccines for multiple strains of the disease 92

Universal influenza vaccines 92

Future prospects of influenza vaccines 92

Application of new technologies for influenza vaccines 93

Adjuvants 93

Cell culture-derived influenza vaccines 94

DNA vaccines for avian influenza 95

Epitope-based vaccines for influenza 95

Gene-based vaccines for influenza 96

Live attenuated vaccines 96

MAbs for passive immunization against avian influenza 96

M2e-based human influenza A vaccine. 96

Pre-pandemic split antigen H5N1 vaccine 97

Recombinant-protein based influenza vaccines 97

Synthetic avian influenza vaccine 98

Viral vectors for influenza vaccination 99

Virus-like particles as influenza vaccines 99

RNAi-based approaches 100

Inhibition of influenza virus by siRNAs 100

Limitations of RNAi approach to influenza 101

Challenges and future prospects of siRNAs for influenza 101

Antisense approaches 102

NEUGENE® antisense for inhibition of multiple strains of influenza A 102

Nanoviricides against influenza 102

Other innovative approaches 103

Abatacept 103

Polymeric coatings to inactivate influenza virus 103

Cytotoxic therapy 103

Cyanovirin 104

Fludase 104

Multiferon® 104

Pyrrolidine dithiocarbamate 105

T-705 105

Value of antivirals in preventing spread of influenza after exposure 105

Resistance to influenza therapy and efforts to overcome it 105

NIAID Centers of Excellence for research on pandemic influenza viruses 106

Research on influenza viruses at Bayer 106

Concluding remarks and future prospects 107

8. AIDS/HIV 109

Introduction 109

Epidemiology 109

Current concepts of pathomechanisms 109

Decoding the structure of an entire HIV genome 110

Genentic basis of resistance against HIV 110

Host-pathogen interactions that regulate HIV-1 replication 110

Pathogenesis of AIDS 111

Visualization of the interaction of HIV-1 proteins with target cells 112

Viral latency in HIV 112

Complications of AIDS 113

AIDS and the nervous system 113

Opportunistic infections in AIDS 113

Coexistent HIV-1 and HSV-2 114

Coexistent hepatitis virus infections with HIV 114

HIV and HBV 115

HIV and HCV 115

AIDS wasting syndrome 116

Current therapies 116

Aim of anti-HIV drugs 117

Efavirenz 118

Tipranavir 118

Enfuvirtide 119

Darunavir 119

Impact of antiretroviral treatment on transmission of HIV 119

Postexposure prophylaxis against HIV 120

Limitations of current therapies 121

Adverse effects of antiretroviral therapy 121

Drug resistance in AIDS 122

Effect of interruption of HIV treatment 123

Reservoirs of HIV Infection 123

Persistance of low-level viremia in HIV-1 patients on retroviral therapy 123

Reconsideration of abandoned therapies for AIDS 123

Therapies in development 123

Drugs in development for HIV/AIDS 124

Nucleoside reverse transcriptase inhibitors 125

Apricitabine 125

Non-nucleoside reverse transcriptase inhibitors 125

Etravirine 125

IDX899 125

Novel protease inhibitors 126

Overcoming HIV-1 resistance to PIs 126

PPL-100 127

Entry inhibitors targeting CCR5 receptor 127

Maraviroc 128

SP-01A 128

MAbs targeting CCR5 receptor 128

PRO 140 129

Ibalizumab 129

Integrase inhibitors 130

Raltegravir (Isentress) 130

Elvitegravir (GS 9137) 131

S/GSK1349572 131

S/GSK1265744 132

Design of fusion inhibitor peptides against enfuvirtide-resistant HIV-1 132

Maturation inhibitors 132

Blocking of pre-integration complex translocation 133

Immune enhancers 133

Pyrimidinediones 133

Novel combinations of drugs for prevention of AIDS 134

Truvada 134

Combination of raltegravir, enfuvirtide, and darunavir 134

Other innovative antiviral approaches against HIV/AIDS 134

Enhancing immune response by blockade of PD-1 receptor 134

IL-2 as adjunct to antiretroviral therapy 135

A filtration device for HIV-1 as an adjunct to the immune system 135

In vitro evaluation of antiviral drug activity 135

Methods for sustaining antiviral activity 136

Selective targeting of ITK to block multiple steps of HIV replication 136

Drugs from natural sources 136

Anti-HIV activity of drugs that stimulate cholesterol efflux 137

Antiviral hyperactivation-limiting therapeutics 137

Blocking of HIV budding by DC-SIGN protein 137

ATR kinase as a target for anti-HIV drug discovery 138

Nanoviricides for HIV/AIDS 138

Prophylactic measures to prevent HIV infection 138

Microbicidal agents for local application in HIV/AIDS 139

Currently investigated microbicidals against HIV and their limitations 139

CCR5 receptor blockers 140

PSC-Rantes and recombinant chemokine analogs 140

HIV-1 entry inhibitor griffithsin as a topical microbicide 141

Nanotechnology-based topical microbicides 141

Next generation microbicides for HIV 141

Intracellular immunization in HIV 142

Engineered cellular proteins such as soluble CD4s 142

Intracellular antibodies 142

Selection of T-cell vaccine antigens 142

Glycoprotein 120 as target for neutralizing HIV-1 antibodies 143

Anti-rev single chain antibody fragment 143

Gene therapy strategies in HIV/AIDS 143

Inhibition of HIV-1 replication by lentiviral vectors 144

VRX496 (Lexgenleucel-T) 144

Insertion of protective genes into target cells 145

Use of genes to chemosensitize HIV-1 infected cells 145

Autocrine interferon-? production by somatic cell gene therapy 145

HIV/AIDS vaccines 145

Cell-based vaccines for HIV 146

Delivery of HIV vaccine by an adenoviral vector 147

DNA vaccines for HIV/AIDS 147

Epitope-based DNA vaccines against HIV 148

Gene transfer for HIV vaccination 149

Limitations and needs of HIV vaccines 149

Recombinant HIV proteins 149

Vaccination after discontinuation of antiretroviral treatment 149

Innovations in HIV/AIDS vaccine 150

Attenuated rabies virus-based vaccine for HIV 150

Combination of a prime vaccine and booster vaccine 150

Dendritic cell-based vaccine for HIV 151

DermaVir 151

Early control of HIV by an effector memory T cell vaccine 151

MVA nef vaccine 152

Peptide-based vaccine for HIV 152

Personalized vaccine for HIV 152

Transdermal nanoparticles for immune enhancement in HIV 152

Vaccine to prevent HIV entry at the mucosal level 153

Cell therapy for HIV/AIDS 153

hESCs converted to T-cells for treatment of HIV infection 153

Transplantation of genetically modified hematopoietic cells 154

Transplantation of genetically modified T cells 154

Overlapping Peptide-pulsed Autologous Cells 155

Antisense approaches to AIDS 155

Antisense oligodeoxynucleotides 155

Antisense efforts with PNA constructs 155

RNA decoys 156

Ribozymes 156

RNAi applications in HIV/AIDS 157

A multiple shRNA approach for silencing of HIV-1 157

Aptamer-mediated delivery of anti-HIV siRNAs 158

Bispecific siRNA constructs 158

Role of the nef gene during HIV-1 infection and RNAi 158

siRNA-directed inhibition of HIV-1 infection 159

Synergistic effect of snRNA and siRNA 159

Targeting CXCR4 with siRNAs 160

Targeting CCR5 with siRNAs 160

Concluding remarks on RNAi approach to HIV/AIDS 161

Companies involved in developing gene therapy for HIV/AIDS 161

Conclusions regarding gene therapy of HIV/AIDS 162

Testing for new anti-HIV therapies 162

Personalized approach to management of HIV 162

Differences in response of the body to HIV 163

Variations in action of drugs on HIV 163

Drug-resistance in HIV 163

Replication Capacity measurement 164

Role of biomarkers in management of HIV/AIDS 164

Prevention of adverse reactions to antiviral drugs 164

Nanoviricides as a personalized approach to HIV 165

Concluding remarks and future prospects 165

9. Hepatitis Viruses 167

Introduction 167

Hepatitis delta virus infection 167

Hepatitis A virus infection 167

Hepatitis E virus infection 168

Epidemiology 168

Structure of the HEV 168

HEV vaccines 168

Epidemiology of HBV 169

Pathogenesis of HBV-induced liver disease 169

Current approaches to management of HBV 170

Entecavir 170

Adefovir dipivoxil 171

Telbivudine 171

Pegylated interferon-alpha 171

Limitations of current therapies and needs of HBV 171

Personalized management of HBV 172

Innovations in the management of HBV 172

Tenofovir disoproxil fumarate 172

Hepatitis B immune globulins 173

Nabi-HB 173

HepaGam B 173

Hepatitis B vaccine composed in a novel nanoemulsion adjuvant 173

Innovative pharmaceuticals for HBV 174

Clevudine 174

HepDirect prodrugs 174

Monoclonal antibodies for HBV 175

RNAi-based therapy of HBV 175

Personalized treatment of hepatitis B 176

Concluding remarks and future prospects of management of hepatitis B 176

Epidemiology of HCV 176

HCV characteristics 177

Pathomechanism of HCV infection 177

Mechanism of HCV entry 177

HCV and the immune system 177

Mechanism of HCV replication and response to interferon 178

Current approaches to management of HCV 178

Interferon therapy for HCV 178

Limitations of current HCV therapies 179

Novel approaches to HCV 179

HCV protease inhibitors 180

Boceprevir 180

Narlaprevir (SCH 900518) 180

Telaprevir (Incivek) 181

Small molecule HCV protease inhibitors 181

Innovations in interferon therapy for HCV 181

AlbIFN-?2b 182

Directed evolution of gene-shuffled IFN-? for treatment of HCV 182

GEA007.1 182

Omega DUROS 182

PEG-IFN-? 183

Personalizing interferon therapy of HCV 183

Innovative ribavirin-based treatments 184

Targeted delivery of hemoglobin-ribavirin conjugate for HCV 184

Taribavirin 184

Nucleoside polymerase inhibitor 184

Valopicitabine 184

Host cell targets for hepatitis C therapy 185

SP-10 185

NS5a inhibitors 186

Compounds targeting HCV receptor E2 186

Cyclophilin inhibitors 186

Alisporivir 187

Methylene blue 187

Naringenin 187

Nitazoxanide 188

Cyclosporine and analogues as anti-HCV agents 188

Clemizole and HCV 189

RNAi-based approaches to HCV 189

Use of adenoviral vectors for RNAi 189

siRNAs for HCV 190

Limitations and drawbacks of siRNA therapy for HCV 190

Role of miRNA in viral infections 191

miR-122 antagonists 191

Therapeutic vaccine for HCV 191

Clinical trials of HCV therapeutics 192

Limitations to the development of effective anti-HCV therapeutics 192

Causes of treatment failure in chronic hepatitis C 192

HCV drug resistance 193

Personalized management of HCV infection 193

Role of sequencing in personalized management of HCV 194

Concluding remarks about HCV therapy 195

Future needs in HCV therapy 195

10. Miscellaneous Commercially Important Virus Infections 197

Introduction 197

Herpes viruses 197

Herpes simplex virus 197

Treatment of HSV-1 197

Acyclovir 197

Vaccines for HSV 198

Antisense therapy for HSV-1 198

Herpes simplex virus 2 and genital herpes 198

Famciclovir 199

Intravaginal microbicidal agents for HSV-2 199

Vaccines for HSV-2 199

Herpes simplex keratitis 200

Herpes simplex encephalitis 200

Limitations of current HSV therapies 201

Herpes zoster virus 201

Herpes zoster and chicken pox 201

Epidemiology of herpes zoster 201

Treatment of herpes zoster 202

Herpes zoster vaccine 202

Cytomegalovirus 202

Valganciclovir hydrochloride 203

T-cell therapy for CMV 203

Vaccine for CMV 203

Gene therapy of CMV 203

Antisense approach to CMV 204

siRNA treatment of CMV 204

Epstein-Barr virus 205

Human papilloma virus 205

Epidemiology 205

Vaccines for HPV 205

Gardasil 206

Cervarix 206

Vaccine based on fusion proteins of HPV envelope 206

DNA vaccine VGX-3100 207

Limitations of HPV vaccines 207

Antivirals for HPV 208

Imiquimod 208

Novel approaches against HPV 208

Intrabody strategies for the treatment of HPV 208

A novel peptide to inhibit HPV 209

Heat shock protein-based antivirals 209

Respiratory syncytial virus 209

Epidemiology 209

Current management of RSV 210

Palivizumab 210

Innovative anti-RSV products in development 210

RSV604 210

MDT-637 210

RNAi approach to RSV 211

Vaccines for RSV 211

BCG as a vaccine against RSV 211

Oral DNA vaccine for RSV 211

Other respiratory viruses 212

Parainfluenzavirus type 3 212

Human metapneumovirus 212

Gastrointestinal viruses 213

Noroviruses 213

Concluding remarks 214

11. Viruses with High Impact but Low Commercial Significance 215

Introduction 215

Chikungunya fever 215

Coxsackie virus 215

Japanese encephalitis 216

Vaccines for JE 216

Parvovirus 217

Polyomavirus JC 217

Rabies 217

Rabies vaccines 218

Recombinant viral vaccines for rabies 218

DNA vaccine against rabies 219

Rabies immune globulin 219

Monoclonal antibodies for rabies 219

NanoViricides approach for rabies 219

The Milwaukee protocol for rabies 220

Rotavirus 220

Epidemiology 220

Vaccines against rotavirus 221

Viral hemorrhagic fevers 221

Dengue 222

Antivirals in development 222

Dengue vaccines 223

Genetic elimination of dengue vector mosquitoes 224

Ebola virus 224

Development of antiviral drugs for Ebola 225

DNA vaccine for Ebola 225

Lassa fever 226

Marburg hemorrhagic fever 226

Yellow fever 227

Vaccines for yellow fever 227

Sequencing of Aedes aegypti genome and control of yellow fever 227

Crimean-Congo hemorrhagic fever 228

West Nile virus 228

Epidemiology 228

Pathogenesis 229

Treatment of West Nile neuroinvasive disease 229

Vaccines against WNV 229

Innovative treatments for WNV 230

Western equine encephalitis 230

Sporadic virus epidemics 230

Coronavirus/severe acute respiratory syndrome 230

Therapeutic approaches to SARS 231

MAbs for SARS 231

siRNA treatment of SARS 232

Zoonotic viral infections 232

Vaccines for zoonotic viral diseases 232

Virus bioterrorism and biowarfare 232

Small pox as a biological weapon 233

Status of small pox vaccination 233

Strategies against virus bioterrorism and biowarfare 234

Increasing resistance by stimulating innate immune mechanisms 234

Nanoviricides for combating viral bioterrorism 234

Concluding remarks 235

12. Markets for Antivirals 237

Introduction 237

Markets according to disease 237

Influenza market 237

HIV/AIDS market 238

Hepatitis B and C markets 239

Markets according to products and approaches 239

Market values of monoclonal antibodies for viral diseases 239

Market values of vaccines for viral diseases 239

Markets for vaccines against HPV 240

Markets for other antiviral vaccines 240

Markets according to geographical areas 241

Emerging markets for antiviral therapeutics 241

Geographical distribution of HIV/AIDS market 242

Unmet needs in antivirals 242

Policies regarding conquered viral diseases 243

Future of polio vaccine 243

Policies concerning HPV vaccine for prevention of cervical cancer 244

HPV vaccine in developing countries 244

Future prospects of innovative approaches 245

US Government support of antiviral efforts 246

US Government support for R & D in avian influenza vaccines 246

US Government support for developing anti-bioterrorism agents 246

The European Union support of antiviral research 247

European Commission's research support for anti-HIV/AIDS programs 247

European Commission's support anti-influenza programs 248

Collaboration of biotechnology companies with big pharma 249

Strategies for marketing 249

13. Companies 251

Introduction 251

Top companies 251

Profiles of pharmaceutical companies 252

Profiles of antiviral companies 268

Profiles of viral vaccine companies 382

Collaborations 450

14. References 457

List of Tables

Table 1 1: A practical classification of viruses 19Table 1 2: Vaccines vs therapeutics for viral diseases 25Table 1 3: Historical landmarks in the development of antiviral therapies 25Table 2 1: Classification of antiviral strategies 27Table 2 2: Viral vs cellular targets for discovery of antivirals 28Table 2 3: Viruses amenable to antisense oligonucleotides 39Table 2 4: Inhibition of viral replication by RNAi 41Table 3 1: Types of vaccines for viral diseases 46Table 4 1: Role of nanobiotechnology in virology 53Table 5 1: Methods of delivery of antiviral agents 59Table 5 2: Role of nanotechnology for improving delivery of antivirals 64Table 5 3: Commercially available liposomal antiviral vaccines 65Table 6 1: SWOT of monoclonal antibodies 71Table 6 2: SWOT of agents that prevention viral entry into cells 72Table 6 3: SWOT of drugs interfering with intracellular replication 72Table 6 4: SWOT of protease inhibitors 72Table 6 5: SWOT of integrase inhibitors 72Table 6 6: SWOT of maturation inhibitors 72Table 6 7: SWOT of neuraminidase inhibitors 73Table 6 8: SWOT of targeting Toll-like receptors (TLRs) 73Table 6 9: SWOT of topical antivirals agents against viral infections 73Table 6 10: SWOT of gene therapy, antisense oligonucleotides, RNAi 73Table 6 11: SWOT of vaccines 73Table 6 12: SWOT of NanoViricides 74Table 7 1: Anti-influenza approaches 81Table 7 2: Antiviral drugs used for influenza 81Table 7 3: Various approaches to production of influenza vaccines 93Table 8 1: Drugs in clinical development for HIV/AIDS 124Table 8 2: Strategies for gene therapy of AIDS 143Table 8 3: Classification of HIV/AIDS vaccines in clinical trials 145Table 8 4: Companies involved in developing gene therapy for HIV/AIDS 161Table 9 1: Innovations in the treatment of HBV 172Table 9 2: Innovations for management of HCV 180Table 9 3: Antiviral agents for HCV targeting host cells 185Table 9 4: HCV drugs in clinical trials 192Table 10 1: Methods of delivery of acyclovir 197Table 11 1: Strategies against virus bioterrorism and biowarfare 234Table 12 1: Worldwide market for all antiviral approaches 2011-2021 237Table 12 2: Markets for antivirals according to virus infections 2011-2021 237Table 12 3: Markets values of all drugs for HIV/AIDS 2011-2021 238Table 12 4: Market values of monoclonal antibodies for viral diseases 2011-2021 239Table 12 5: Market values of vaccines for viral diseases 2011-2021 240Table 12 6: Markets for antiviral drugs according to geographical areas 2011-2021 241Table 12 7: Markets for antiviral vaccines according to geographical areas 2011-2021 241Table 12 8: Emerging markets for antiviral drugs according to countries 2011-2021 241Table 12 9: Emerging markets for antiviral vaccines according to countries 2011-2021 242Table 13 1: Top five antiviral companies 251Table 13 2: Roche antiviral products in development 258Table 13 3: Collaborations of antiviral companies 450

List of Figures

Figure 1 1: Varieties of host and cell responses to viral infections 21

Figure 1 2: Cycle of infection and replication of a retrovirus 22

Figure 1 3: Viral-induced cancer 24

Figure 2 1: An integrated approach to viral diseases 42

Figure 4 1: Schematic representation of NanoViricide attacking a virus particle 57

Figure 7 1: Evolution of mutations associated with virulence/drug resistance in H5N1 78

Figure 7 2: Mechanism of development of resistance to oseltamivir 84

Figure 8 1: Mode of action of some current anti-HIV drugs 117

Figure 9 1: Steps of HBV replication and site of action of various drugs 169

Figure 9 2: Omega DUROS device for interferon delivery in chronic hepatitis C 183

Figure 12 1: Unmet needs in antivirals 243

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