Lead Identification & Optimisation

	Results provided by Lab21 have successfully sup- ported IND applications by companies progressing their HIV and HCV anti-viral therapies into clinical evaluation.

• HIV
• HCV
• Artificial HCV replication systems  
• Herpes viruses
• Respiratory viruses
• Broad spectrum antiviral screen
• Drug combination studies
• Cellular toxicity

                                                                                                                  
HIV                                                                                                          Back to Top
                                      
Primary strains

We have extensive experience in the propagation and characterisation of HIV clinical isolates.

• Primary isolates are replicated or a limited number of passages in PBMC culture
• Exemplary model for HIV infection in man
• Most meaningful results when utmost clinical relevance is required
• Diverse clades
• Access to currently circulating multi-drug resistant strains
• Tropism analysis (CCR5/CXCR4)

Laboratory strains

We work with a large bank of lab adapted HIV strains.

• Disparate genotypes and phenotypes
• Fully characterised panels can be assembled on the basis of clade, sequence, drug resistance, etc.

The search for new anti-virals against the majority of human viruses is carried out by studying the ability of the viruses to grow in the laboratory in the presence of the new drugs. Unfortunately some viruses, including hepatitis C virus (HCV), do not grow well in the laboratory, so this approach is impractical. Consequently antiviral drug discovery for HCV depends on the use of either related (surrogate) virus assays or artificial replicon systems. We offer both of these as alternatives for characterisation of drug candidates.

Surrogate virus systems

• Bovine Viral Diarrhoea Virus (Pestivirus)
• Yellow Fever Virus (Flavivirus)

We also provide alternative surrogate virus systems if required (for example Dengue & West Nile
Fever), and offer simple range finding activity assays or detailed drug titrations.



Subgenomic replicons     

The FDA recommends the use of HCV replicon systems to establish anti-viral activity and  to provide anti-viral resistance data.

 

Replicon systems are artificial replicating systems derived from recombinant DNA copies of the viral genome.

Subgenomic replicons represent all the replicative functions of the virus but do not assemble viral particles so are non-infectious systems.

We offer genotype 1a and 1b systems available representing the most prevalent strains in Western Europe and North America. This genotype is also the most refractory to current standards of treatment. Our systems are amenable for use with both small molecule candidates and biopharmaceuticals.

Infectious Replicon

In 2006 the artificial replicon system was significantly enhanced by the construction of full-length genomic replicons representing all stages of the viral life cycle (Yi et al, PNAS, 103, 2310-5).

Such systems obviously generate infectious virus so can only be studied under stringent containment conditions. These systems are only available in a limited number of laboratories throughout the world, and Lab21 is one of the few commercial companies with access to such an infectious replicon system.

All single and multiple drug combination studies can be undertaken as for subgenomic replicons.


Herpes viruses                                                                                                               Back to Top

Anti-viral services for the majority of human herpes viruses including HSV-1, HSV-2, VZV and CMV are available. We have considerable experience in the development of new drugs for herpes virus therapy:

• HSV genotyping (PCR)
• Plaque assay for viral quantification and anti-viral activity determination
• qPCR viral quantification for anti-viral activity determination
• Genetic strain profiling

Respiratory viruses offer a commercially attractive target for drug development encompassing diverse conditions from the common cold to influenza (including H5N1). We utilise state-of-the-art molecular technology to screen for the majority of respiratory pathogens as well as biological assays to identify new anti-viral agents against those pathogens.

In addition to standard biological screens for anti-viral activity, we have also developed a series of semi-quantitative PCR assays offering unsurpassed sensitivity and linearity for determining therapeutic efficacy.






















We routinely propagate a wide range of viruses to enable in-depth studies on drugs targeting a wide range of commercially important diseases.

We can identify antiviral activity of new compounds at the earliest stages of lead development by screening molecules against a diverse panel of viruses including:

• BVDV, FluA, FluB, HIV, HSV-1 & 2, HRV, RSV and Yellow Fever
• Other organisms up to and including Cat III handling available on request

The need to study the behaviour of a new drug or drug candidate in combination is clearly evident from the current strategy for the treatment of HIV and HCV. A favourable interaction is the goal when seeking to bring new drugs to the market, and the use of cell culture models provides a key means to identify this.

• Dual and triple drug combinations
• Detailed analysis of results upon request
• Wide variety of compounds available at Lab21 to use in manufacturer-independent studies

We routinely include cell viability assays in parallel with in vitro antiviral screening studies to report a balance of compound efficacy against cytotoxicity.

• Studies conducted in uninfected cells
• Indicate potential drug tolerability problems & possible undesired effects in later trials