Challenge: Infection with herpes viruses is associated with several immunodeficient human diseases including the development of cancers. Patients receiving organ transplants are particularly sensitive to such infections. These patients are treated with antiviral agents; however, approved drugs are often associated with severe side effects and the development of resistance can compromise therapy. There is thus an urgent need to discover novel antiviral agents that target the various members of the herpes virus family.
Solution: The aim of this project was to develop a rapid screening platform for compounds displaying broad spectrum antiviral activity against all eight major human herpesviruses. The team used a phage-based approach to produce common portions of herpes virus DNA polymerases. These novel phage/virus chimeric polymerases can be viewed as herpesvirus orthologs. These enzymes are produced in high quantities to facilitate enzyme screening.
Achievements/Impact: The phage-based high-throughput screening platform developed during this project offers low cost screening potential for novel antivirals with broad-spectrum activity against all members of the herpes virus family. The team also validated antiviral drug susceptibility tests for Epstein-Barr virus (EBV), human herpes virus 6 and 8 (HHV-6 and HHV-8) using real-time PCR-based assays as well as antiviral drug toxicity assays on relevant cell lines. The technology has been integrated within the R&D discovery process of at least one CQDM pharma member.
Principal Investigator Matthias Götte McGill University |
Co-investigator Guy Boivin Université Laval |
Completed Project |
$1,340,000 / 3 years |
Supported by CQDM through: – Merck – Pfizer – AstraZeneca – MESI – BL-NCE |