Innovations in Combating Infectious Diseases

Date: June 22, 2010
Pages: 250
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Publisher: Business Insights
Report type: Strategic Report
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Innovations in Combating Infectious Diseases
Innovations in Combating Infectious Diseases: Opportunities in Therapeutics and Diagnostics Through Application of Proteomics, Genomics, Nanotechnology, and Novel Sources of Lead Generation

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 mportant 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?

Innovations in Combating Infectious Diseases
Executive summary
The need for new therapeutic approaches in infectious diseases
Proteomics in the design of novel diagnostics for infectious diseases
Proteomic methods in infectious disease drug discovery
Genomics and its impact on drug discovery in infectious diseases
Natural sources of drug leads for infectious diseases
Lead optimization in infectious disease drug discovery
Applications of nanotechnology in infectious diseases

CHAPTER 1 THE NEED FOR NEW THERAPEUTIC APPROACHES IN INFECTIOUS DISEASES

Summary
Introduction
Why do we need continuing drug development?
Major areas of unmet need in infectious disease
Report scope

CHAPTER 2 PROTEOMICS IN THE DESIGN OF NOVEL DIAGNOSTICS FOR INFECTIOUS DISEASES

Summary
Introduction
An overview of techniques in proteomics
Separation techniques
Two-dimensional gel electrophoresis (2D-GE)
Separation using SELDI Protein Chip technology
Identification techniques
Mass spectrometry
Bottom up and top down techniques
Targeted proteomics using western blots and MS
Antibody and aptamer microarray technology in proteomics
Allied technology: glycan arrays
Limitations of proteomic techniques
Limitations of MALDI-TOF
The need to be aware of artifacts
The limitations of shotgun proteomics
MALDI approaches – profiling and imaging
Protein, antibody, and aptamer arrays
Diagnostics in infectious diseases using proteomic techniques
Bacterial infections, proteomics, and diagnosis
MRSA and community- and hospital-acquired infections
Diagnosing bacterial meningitis and conjunctivitis
Faster and easier diagnosis of tuberculosis
Proteomics in the diagnosis of periodontal disease
Proteomics in the detection of bacteria that pose bioterrorist threats
Using proteome microarrays to identify plague
Diagnosis of anthrax using the host blood proteome
Parasitic infections, proteomics, and diagnosis
Developing diagnostic biomarkers for parasitic infections
Proteomic diagnostics for fungal infections
Proteomics in the detection of viral infections
SARS diagnosis using proteomics
Hepatitis prognosis using proteomics
New diagnostics for prion diseases
Conclusions

CHAPTER 3 PROTEOMIC METHODS IN INFECTIOUS DISEASE DRUG DISCOVERY

Summary
Introduction
Proteomics in target identification and lead discovery in infectious diseases
Using proteomics in drug discovery for parasitic diseases
Malaria – using proteomics to map parasitic gene expression
Liver fluke infections
Echinococcus multilocularis
Leishmaniasis
Entamoeba histolytica
Proteomics and antiviral discovery
HIV

Influenza
Hepatitis B
Proteomics in the discovery of novel antibacterial drug targets
Drug discovery for nosocomial infections
Targeting bacteria that affect the gut
Applying proteomics to rare bacterial diseases
Proteomics and drug discovery for bacterial meningitis
Proteomics and drug discovery in tuberculosis
Potential therapeutics for bioterrorist threats
Proteomics in antifungal drug discovery
Proteomics in the generation of new vaccine candidates
Antibacterial vaccines
Towards a new vaccine for tuberculosis
Antibiotic strains of Staphylococcus aureus
Clostridium difficile
Fungal vaccines
Parasitic vaccines
Leishmania amastigotes
Toxoplasma gondii
Schistosomiasis
Malaria
Viral vaccines
Proteomics and HIV vaccine approaches
Influenza vaccine strategies
Conclusions

CHAPTER 4 GENOMICS AND ITS IMPACT ON DRUG DISCOVERY IN INFECTIOUS DISEASES

Summary
Introduction
Using genomics to identify new drug targets in infectious diseases
Using genomics to target pathogen factors
Ligand-based chemogenomic approaches
Using genomics to target host factors
Novel genomic approaches to therapeutics in infectious diseases
RNA interference
Ribozymes and flexizymes
Replicons
Genomics in antiviral drug discovery
Genomics and influenza
Background to influenza
Key development areas
How genomics can be applied
Genomics and HIV
Background to HIV
Key development areas
Genomics and flavivirus infection
Background to flaviviruses
Key development areas
Genomics and hepatitis C
Background to hepatitis C
Key development areas
Genomics and emerging viral disease
SARS-associated coronavirus
Nipah virus
Dengue
Genomics in antibacterial drug discovery
General approaches to the discovery of new antibiotics
Targeting metabolic networks
Genomics in antiparasitic drug discovery
Malaria
In silico profiling and novel antimalarial candidates
Targeting host cell factors
Evolutionary patterning
Kinetoplastid diseases
Toxoplasmosis
Schistosomiasis
Key development areas
Genomic characterization of parasitic pathogens
Trypanosomatids
Malaria
Schistosomiasis
Genomics in antifungal drug discovery
Genomic insights into prion diseases
Genomics in epidemiological surveillance and monitoring
Genomic strategies for designing novel infectious disease vaccines
Terrorist activity with bioagents: genomic and combined strategies for control
Conclusions

CHAPTER 5 NATURAL SOURCES OF DRUG LEADS FOR INFECTIOUS DISEASES

Summary
Introduction
Drugs from natural sources worldwide
Asia and Africa Science Platform Program
Japan–China Joint Medical Workshop on Drug Discoveries and Therapeutics 2008
Drugs from China
Drugs from natural sources: research in other developing countries
Yemen
Cameroon
Kenya
Nigeria
Brazil
Peru
Antibiotics from natural sources
Antibacterials from plants
Antimicrobials from endophytes
Antimicrobials from other sources
Antiviral drugs from natural sources
Potential of phenolics of natural origin as anti-HIV agents
Medicinal plant extracts and activity against herpes simplex
Effect of sulfated astragalus polysaccharide on the cellular infectivity of infectious bursal disease virus
Antiviral compound derived from the plant Melia azedarach
Antifungal drugs from natural sources
Antifungal agents derived from plants
Activity of isoxazolidinone-containing compounds in the treatment of serious mycoses
Antiparasitic agents from natural sources
Artemisinin
Other antimalarial drug candidates from natural sources
Plant-derived antimalarial agents: new leads and efficient
phytomedicines
Cytotoxic and antiplasmodial compounds from the roots of
Strophioblachia fimbricalyx
Antiplasmoidal alkaloids from Cassia siamea
Marine actinomycetes against human malaria
Non-malarial parasitic diseases: leishmania and trypanosomes
Biosurfactants and derivation from natural sources
Potential applications of biosurfactants in medicine
Probiotic bacteria and biosurfactants for nosocomial infection control
Antimicrobial biosurfactants from marine Bacillus circulans
Pseudomonas aeruginosa rhamnolipids disperse Bordetella
bronchiseptica biofilms

CHAPTER 6 LEAD OPTIMIZATION IN INFECTIOUS DISEASE DRUG DISCOVERY

Summary
Introduction
What is lead optimization?
How is lead optimization conducted?
Lead optimization is a cyclical process
New drugs for old
Lead optimization can make or break drug discovery
The outcome of the lead optimization process
Techniques used in lead optimization
Lead optimization in infectious diseases
In silico tools
Using in silico tools in drug discovery for tuberculosis
Using in silico tools in drug discovery for malaria
Using in silico tools in HIV drug discovery
High content cellular imaging in infectious diseases
Application to bacterial diseases
Toxicogenomics-based assays in infectious diseases
What is the difference between toxicogenetics and toxicogenomics?
Genetic susceptibility factors in infectious diseases
Crystallographic approaches in infectious diseases
Antibiotic drug discovery
HIV drug discovery
Intelligent design in infectious diseases
Partnerships, databases, and networks
The TDR Drug Targets Database
TDR Activities
TDR achievements and goals
The Helminth Drug Initiative
HDI activities
HDI achievements and goals
The Drugs for Neglected Diseases initiative (DNDi)
DNDi achievements to date
Conclusions

CHAPTER 7 APPLICATIONS OF NANOTECHNOLOGY IN INFECTIOUS DISEASES

Summary
Introduction
The use of nanotechnology in diagnosis
Quantum dot probes
Synthetic polymers
Nanochips
The use of nanotechnology in novel therapeutics for infectious diseases
Novel delivery methods for antibiotics
Using bacteriophages to deliver drugs
Targeting of bacteriophage systems using polymeric nanostructures
Aerosol delivery systems
Photodynamic therapy systems
Nanoemulsions and nanoparticles
Biofilms
Biofilm infections in cystic fibrosis
Biofilm infections related to catheters
Biofilm infections on prosthetic devices
Novel therapeutic development strategies
Peptide therapeutics
Use of nanotechnology to combat tuberculosis
Use nanotechnology to combat pneumonia
Use of nanotechnology to combat malaria
Use of nanotechnology to combat Sin Nombre hantavirus infection
Using nanotechnology to target fungal infections
Candidiasis
New nanovaccine strategies for infectious diseases
Delivering nanovaccines by injection
Mucosal delivery
Gene vaccines
Novel drug delivery using nanotechnology
Nanotubes
Polyphosphazenes and delivery of vaccine antigens
Solid lipid nanoparticles
Conclusions
APPENDIX

Bibliography
Chapter 1
Chapter 2
Chapter 3
Chapter 4
Chapter 5
Chapter 6
Chapter 7
Glossary
Index
LIST OF FIGURES

Figure 2.1: Overview of proteomics
Figure 2.2: Standard proteomic approaches
Figure 2.3: Two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) workflow
Figure 2.4: Example of SELDI-TOF workflow
Figure 2.5: Sites of the body usually affected by MSRA infections
Figure 2.6: Pulmonary TB
Figure 2.7: Trichonomas vaginalis in a Pap smear
Figure 3.8: Distribution of proteins produced at different life-cycle stages of Plasmodium falciparum
Figure 3.9: Clostridium difficile colonies on a blood agar plate
Figure 4.10: Structure–activity relationship homology flowchart
Figure 4.11: Novel antiviral strategies based on the HCV life cycle
Figure 4.12: Target identification via pathogen and host genome sequencing
Figure 4.13: Emergence of MRSA in the US
Figure 4.14: Phylogenetic reconstruction based on orthologous glycerol kinase sequences
Figure 4.15: Timeline of antifungal drug development
Figure 6.16: Summary of techniques used in lead optimization
Figure 6.17: Attrition rates and current drug R&D pipeline for neglected diseases
Figure 7.18: Relationship of nanobiotechnology to nanomedicine and other biotechnologies
Figure 7.19: Schematic representation of a drug-carrying bacteriophage
Figure 7.20: Biofilm maturation
Figure 7.21: Single-walled carbon nanotube bundles (SWNT) with adsorbed antibody presenting that antibody to T-cells
LIST OF TABLES

Table 2.1: Advantages and disadvantages of SELDI
Table 2.2: Advantages and disadvantages of MALDI
Table 2.3: Deaths in the UK annually since 1990 from CJD of all known causes 57
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