Smallpox Antiviral Drug
Abstract
Smallpox virus is considered one of the most significant threats for use as a biowarfare agent. Due to complications from vaccination, mass immunization of the populace is contra-indicated. Our current research seeks to develop effective anti-poxvirus drug(s). Using vaccinia virus (VV) as a model system, the goal of our currently funded work is to determine whether the 17L cysteine proteinase or the 17L metalloproteinase encoded by VV is the pox virus core protein proteinase (vCPP) that is essential for viral maturation and production of infectious progeny. We have recently demonstrated that the 17L cysteine proteinase is the vCPP (Byrd et al., 2002) and will continue to study the role of this enzyme during virus growth. Given this information however, we are also positioned to launch a concerted effort to identify and develop 17L inhibitors as candidate antiviral drugs. The specific goals of the experiments outlined in this report are to: 1) Over-express and purify enzymatically-active 17L proteins; 2) Develop both biochemical and tissue culture assays to measure 17L activity; 3) Utilize a combination of rational drug design and high throughput screening procedures to identify potential 17L inhibitors; and 4) To test candidate inhibitors for their ability to inhibit poxvirus replication in infected cells and appropriate animal models. Successful completion of these experiments will identify 17L inhibitors that can be advanced into pre-clinical and clinical development as antiviral drugs. Such drugs will be an essential addition to our pharmaceutical armamentarium against the deliberate or accidental introduction of a pathogenic poxvirus into our environment in order to protect members of the armed forces or the general populace.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2005
- Accession Number
- ADA430565
Entities
People
- Dennis E. Hruby
- Tove C. Bolken