Reportlinker Adds Innovations in Combating Infectious Diseases: Opportunities in Therapeutics and Diagnostics Through Application of Proteomics, Genomics, Nanotechnology, and Novel Sources of Lead Generation

NEW YORK, July 6 /PRNewswire/ -- Reportlinker.com announces that a new market research report is available in its catalogue:

Innovations in Combating Infectious Diseases: Opportunities in therapeutics and diagnostics through application of proteomics, genomics, nanotechnology, and novel sources of lead generation

http://www.reportlinker.com/p0233956/Innovations-in-Combating-Infectious-Diseases-Opportunities-in-therapeutics-and-diagnostics-through-application-of-proteomics-genomics-nanotechnology-and-novel-sources-of-lead-generation.html

Infectious disease is not merely a problem of the past; despite significant breakthroughs achieved during the last century in the development of antibiotic, antiviral, and antiparasitic drugs and vaccines, the eradication or even control of many infectious diseases has not been accomplished. Of particular current concern are the problems of rapidly developing drug resistance, emerging disease, re-emerging disease, the threat of bioterrorism, and the speed of reaction to the appearance of virulent strains posing pandemic threats. Furthermore, the effective treatment of infectious diseases is dependent on accurate and rapid diagnosis, and this in itself can present significant challenges, especially in cases where the disease progression is poorly understood or has long asymptomatic latency (such as prion diseases).

Successful drugs and vaccines against infectious agents that put millions of people at risk have potentially lucrative markets. The key to developing those drugs is to understand the pathogenic process and gain insight into where and how it can best be interrupted. This report makes a detailed and comprehensive analysis of the cutting edge of research aiming to reveal how bacteria, viruses, fungi, and prions infect and affect their hosts. It also assesses the new technologies and techniques that are being used to design and develop the anti-infective drugs and diagnostic methods of the 21st century.

Key features of this report

This report presents a snapshot of how new technologies and approaches are being applied to the discovery of new drug targets, vaccine candidates, lead compounds, and novel delivery systems that will enhance diagnostics and therapeutics across the whole range of infectious diseases:

- How proteomics is being used to identify biomarkers for new diagnostics in infectious diseases

- How proteomics is being used to identify novel targets for drug discovery and vaccine development in infectious diseases

- The impact of genomics on the search for novel targets for infectious disease drug discovery

- Novel natural sources for lead generation in infectious diseases

- Lead optimization techniques relevant to infectious diseases

- How the application of nanobiotechnology is impacting on drug discovery and drug delivery in infectious diseases

Scope of this report

- Gain awareness of the most significant areas of unmet need for anti-infective drug development.

- Build knowledge of the most promising diagnostics research – ripe for commercialization – for MRSA and community-acquired infections, bacterial meningitis, periodontal disease, and innovative ways for predicting outcome in hepatitis infections.

- Discover how proteomics and genomics are making an increasing impact on drug development programs, and how important infectious agents can be tackled by drug and vaccine approaches.

- Identify the new opportunities for small and large biotechnology based companies to undertake vaccine development based on proteomic and genomic studies

Key Market Issues

- More accurate and rapid diagnostics will remain a pressing need combating prion diseases, sexually transmitted diseases, HIV, hospital-acquired infections and bioterrorism threats.

- Diagnostics is a big area that is ripe for more commercial development, particularly for diagnostic kits that are fast and simple to operates by unskilled personnel, making them amenable to the point-of-care use.

- Personalized medicine will remain a priority; drug treatments need to be more tailored and efficient with fewer side effects, less frequent dosing, and faster action..

- Using genomics to monitor and carry out surveillance of infectious disease will become more important and more necessary, so that new outbreaks, spread of disease, and danger of pandemics can be better monitored and predicted by global warning systems.

- The need to identify, monitor, and respond to bioterrorism will continue to drive research into lethal viral infections such as small pox and ebola, and bacterial diseases such as anthrax and plague.

Key findings from this report

- Drug development, vaccine development, and novel approaches to therapeutics are needed urgently for bacterial, viral, fungal, and prion diseases, which cause high morbidity and mortality in both the developing and the developed world.

- To date, there has been an intensive research effort to use proteomics to detect, identify, characterize, and validate biomarkers and protein signatures in diagnostics for many different infectious diseases but validation and commercialization has so far proved relatively elusive.

- Drug resistance, emerging infections and the threat of bioterrorism make the understanding of virulence factors and disease pathogenesis essential to form a springboard from which to launch drug discovery programs.

- Genomics is being applied to drug discovery across the spectrum of infectious diseases, whether they are caused by bacteria, viruses, fungi, parasites, or prions. Genomic data can be used in public health surveillance and monitoring of infectious diseases, particularly when there is a threat of a pandemic or bioterrorist attack.

- Novel sources of lead compounds to screen against newly discovered targets are much needed; natural sources have already provided the starting point for several successful anti-infectives, and many sources remain to be explored.

Key questions answered

- Which areas of drug development in infectious disease could have the greatest impact?

- How can the relatively new technology of proteomics be used to develop leads for drug development?

- How are proteomic techniques being used in the design and production of modern diagnostic tools for infectious diseases?

- How are genomic technologies changing the way lead compounds are generated and providing ideas for innovative targeted drugs?

- In which bacteria, viral, fungal and prion diseases are fundamental research efforts showing the most potential for identifying compounds suitable for drug development?

Table of Contents

Innovations in Combating Infectious Diseases

Executive summary 12

The need for new therapeutic approaches in infectious diseases 12

Proteomics in the design of novel diagnostics for infectious diseases 12

Proteomic methods in infectious disease drug discovery 14

Genomics and its impact on drug discovery in infectious diseases 15

Natural sources of drug leads for infectious diseases 16

Lead optimization in infectious disease drug discovery 17

Applications of nanotechnology in infectious diseases 17

Chapter 1 The need for new therapeutic approaches in infectious diseases 20

Summary 20

Introduction 20

Why do we need continuing drug development? 20

Major areas of unmet need in infectious disease 21

Report scope 22

Chapter 2 Proteomics in the design of novel diagnostics for infectious diseases 24

Summary 24

Introduction 25

An overview of techniques in proteomics 26

Separation techniques 28

Two-dimensional gel electrophoresis (2D-GE) 28

Separation using SELDI Protein Chip technology 30

Identification techniques 31

Mass spectrometry 31

Bottom up and top down techniques 32

Targeted proteomics using western blots and MS 33

Antibody and aptamer microarray technology in proteomics 33

Allied technology: glycan arrays 34

Limitations of proteomic techniques 34

Limitations of MALDI-TOF 34

The need to be aware of artifacts 35

The limitations of shotgun proteomics 36

MALDI approaches – profiling and imaging 37

Protein, antibody, and aptamer arrays 38

Diagnostics in infectious diseases using proteomic techniques 39

Bacterial infections, proteomics, and diagnosis 40

MRSA and community- and hospital-acquired infections 40

Diagnosing bacterial meningitis and conjunctivitis 43

Faster and easier diagnosis of tuberculosis 44

Proteomics in the diagnosis of periodontal disease 45

Proteomics in the detection of bacteria that pose bioterrorist threats 46

Using proteome microarrays to identify plague 46

Diagnosis of anthrax using the host blood proteome 47

Parasitic infections, proteomics, and diagnosis 47

Developing diagnostic biomarkers for parasitic infections 48

Proteomic diagnostics for fungal infections 51

Proteomics in the detection of viral infections 53

SARS diagnosis using proteomics 54

Hepatitis prognosis using proteomics 54

New diagnostics for prion diseases 56

Conclusions 61

Chapter 3 Proteomic methods in infectious disease drug discovery 64

Summary 64

Introduction 65

Proteomics in target identification and lead discovery in infectious diseases 65

Using proteomics in drug discovery for parasitic diseases 65

Malaria – using proteomics to map parasitic gene expression 65

Liver fluke infections 68

Echinococcus multilocularis 69

Leishmaniasis 69

Entamoeba histolytica 69

Proteomics and antiviral discovery 70

HIV 70

Influenza 70

Hepatitis B 71

Proteomics in the discovery of novel antibacterial drug targets 71

Drug discovery for nosocomial infections 71

Targeting bacteria that affect the gut 73

Applying proteomics to rare bacterial diseases 74

Proteomics and drug discovery for bacterial meningitis 75

Proteomics and drug discovery in tuberculosis 76

Potential therapeutics for bioterrorist threats 77

Proteomics in antifungal drug discovery 77

Proteomics in the generation of new vaccine candidates 79

Antibacterial vaccines 79

Towards a new vaccine for tuberculosis 79

Antibiotic strains of Staphylococcus aureus 81

Clostridium difficile 81

Fungal vaccines 83

Parasitic vaccines 84

Leishmania amastigotes 84

Toxoplasma gondii 84

Schistosomiasis 84

Malaria 85

Viral vaccines 85

Proteomics and HIV vaccine approaches 86

Influenza vaccine strategies 86

Conclusions 87

Chapter 4 Genomics and its impact on drug discovery in infectious diseases 90

Summary 90

Introduction 91

Using genomics to identify new drug targets in infectious diseases 91

Using genomics to target pathogen factors 93

Ligand-based chemogenomic approaches 93

Using genomics to target host factors 95

Novel genomic approaches to therapeutics in infectious diseases 95

RNA interference 95

Ribozymes and flexizymes 96

Replicons 96

Genomics in antiviral drug discovery 97

Genomics and influenza 97

Background to influenza 97

Key development areas 98

How genomics can be applied 99

Genomics and HIV 99

Background to HIV 99

Key development areas 100

Genomics and flavivirus infection 101

Background to flaviviruses 101

Key development areas 101

Genomics and hepatitis C 102

Background to hepatitis C 102

Key development areas 103

Genomics and emerging viral disease 105

SARS-associated coronavirus 106

Nipah virus 107

Dengue 107

Genomics in antibacterial drug discovery 108

General approaches to the discovery of new antibiotics 109

Targeting metabolic networks 109

Genomics in antiparasitic drug discovery 110

Malaria 110

In silico profiling and novel antimalarial candidates 111

Targeting host cell factors 112

Evolutionary patterning 112

Kinetoplastid diseases 114

Toxoplasmosis 114

Schistosomiasis 115

Key development areas 115

Genomic characterization of parasitic pathogens 116

Trypanosomatids 117

Malaria 117

Schistosomiasis 117

Genomics in antifungal drug discovery 118

Genomic insights into prion diseases 119

Genomics in epidemiological surveillance and monitoring 119

Genomic strategies for designing novel infectious disease vaccines 120

Terrorist activity with bioagents: genomic and combined strategies for control 122

Conclusions 123

Chapter 5 Natural sources of drug leads for infectious diseases 126

Summary 126

Introduction 127

Drugs from natural sources worldwide 129

Asia and Africa Science Platform Program 130

Japan–China Joint Medical Workshop on Drug Discoveries and Therapeutics

2008 130

Drugs from China 132

Drugs from natural sources: research in other developing countries 133

Yemen 133

Cameroon 133

Kenya 133

Nigeria 134

Brazil 134

Peru 134

Antibiotics from natural sources 135

Antibacterials from plants 136

Antimicrobials from endophytes 136

Antimicrobials from other sources 138

Antiviral drugs from natural sources 139

Potential of phenolics of natural origin as anti-HIV agents 140

Medicinal plant extracts and activity against herpes simplex 140

Effect of sulfated astragalus polysaccharide on the cellular infectivity of infectious bursal disease virus 140

Antiviral compound derived from the plant Melia azedarach 141

Antifungal drugs from natural sources 141

Antifungal agents derived from plants 141

Activity of isoxazolidinone-containing compounds in the treatment of serious mycoses 141

Antiparasitic agents from natural sources 142

Artemisinin 142

Other antimalarial drug candidates from natural sources 143

Plant-derived antimalarial agents: new leads and efficient

phytomedicines 143

Cytotoxic and antiplasmodial compounds from the roots of

Strophioblachia fimbricalyx 144

Antiplasmoidal alkaloids from Cassia siamea 144

Marine actinomycetes against human malaria 144

Non-malarial parasitic diseases: leishmania and trypanosomes 144

Biosurfactants and derivation from natural sources 145

Potential applications of biosurfactants in medicine 145

Probiotic bacteria and biosurfactants for nosocomial infection control 145

Antimicrobial biosurfactants from marine Bacillus circulans 145

Pseudomonas aeruginosa rhamnolipids disperse Bordetella

bronchiseptica biofilms 145

Chapter 6 Lead optimization in infectious disease drug discovery 148

Summary 148

Introduction 149

What is lead optimization? 149

How is lead optimization conducted? 149

Lead optimization is a cyclical process 150

New drugs for old 151

Lead optimization can make or break drug discovery 152

The outcome of the lead optimization process 152

Techniques used in lead optimization 153

Lead optimization in infectious diseases 155

In silico tools 155

Using in silico tools in drug discovery for tuberculosis 155

Using in silico tools in drug discovery for malaria 157

Using in silico tools in HIV drug discovery 158

High content cellular imaging in infectious diseases 159

Application to bacterial diseases 159

Toxicogenomics-based assays in infectious diseases 160

What is the difference between toxicogenetics and toxicogenomics? 161

Genetic susceptibility factors in infectious diseases 162

Crystallographic approaches in infectious diseases 162

Antibiotic drug discovery 162

HIV drug discovery 163

Intelligent design in infectious diseases 164

Partnerships, databases, and networks 165

The TDR Drug Targets Database 165

TDR Activities 166

TDR achievements and goals 166

The Helminth Drug Initiative 167

HDI activities 167

HDI achievements and goals 167

The Drugs for Neglected Diseases initiative (DNDi) 167

DNDi achievements to date 168

Conclusions 169

Chapter 7 Applications of nanotechnology in infectious diseases 172

Summary 172

Introduction 173

The use of nanotechnology in diagnosis 175

Quantum dot probes 175

Synthetic polymers 176

Nanochips 176

The use of nanotechnology in novel therapeutics for infectious diseases 176

Novel delivery methods for antibiotics 177

Using bacteriophages to deliver drugs 177

Targeting of bacteriophage systems using polymeric nanostructures 178

Aerosol delivery systems 179

Photodynamic therapy systems 179

Nanoemulsions and nanoparticles 180

Biofilms 181

Biofilm infections in cystic fibrosis 182

Biofilm infections related to catheters 183

Biofilm infections on prosthetic devices 183

Novel therapeutic development strategies 184

Peptide therapeutics 184

Use of nanotechnology to combat tuberculosis 184

Use nanotechnology to combat pneumonia 185

Use of nanotechnology to combat malaria 185

Use of nanotechnology to combat Sin Nombre hantavirus infection 186

Using nanotechnology to target fungal infections 186

Candidiasis 186

New nanovaccine strategies for infectious diseases 187

Delivering nanovaccines by injection 187

Mucosal delivery 188

Gene vaccines 189

Novel drug delivery using nanotechnology 190

Nanotubes 190

Polyphosphazenes and delivery of vaccine antigens 192

Solid lipid nanoparticles 192

Conclusions 192

Appendix 195

Bibliography 195

Chapter 1 195

Chapter 2 196

Chapter 3 203

Chapter 4 209

Chapter 5 220

Chapter 6 227

Chapter 7 232

Glossary 240

Index 249

List of Figures

Figure 2.1: Overview of proteomics 26

Figure 2.2: Standard proteomic approaches 27

Figure 2.3: Two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) workflow 29

Figure 2.4: Example of SELDI-TOF workflow 30

Figure 2.5: Sites of the body usually affected by MSRA infections 41

Figure 2.6: Pulmonary TB 44

Figure 2.7: Trichonomas vaginalis in a Pap smear 51

Figure 3.8: Distribution of proteins produced at different life-cycle stages of Plasmodium falciparum 67

Figure 3.9: Clostridium difficile colonies on a blood agar plate 82

Figure 4.10: Structure–activity relationship homology flowchart 94

Figure 4.11: Novel antiviral strategies based on the HCV life cycle 104

Figure 4.12: Target identification via pathogen and host genome sequencing 106

Figure 4.13: Emergence of MRSA in the US 108

Figure 4.14: Phylogenetic reconstruction based on orthologous glycerol kinase sequences 113

Figure 4.15: Timeline of antifungal drug development 118

Figure 6.16: Summary of techniques used in lead optimization 154

Figure 6.17: Attrition rates and current drug R&D pipeline for neglected diseases 169

Figure 7.18: Relationship of nanobiotechnology to nanomedicine and other biotechnologies 173

Figure 7.19: Schematic representation of a drug-carrying bacteriophage 178

Figure 7.20: Biofilm maturation 181

Figure 7.21: Single-walled carbon nanotube bundles (SWNT) with adsorbed antibody presenting that antibody to T-cells 191

List of Tables

Table 2.1: Advantages and disadvantages of SELDI 31

Table 2.2: Advantages and disadvantages of MALDI 38

Table 2.3: Deaths in the UK annually since 1990 from CJD of all known causes 57

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