At least 20 million people in the US alone are infected with human papillomaviruses, which are associated with a wide range of pathologies, including external cutaneous warts, genital condylomata and cervical carcinoma. Nonetheless, there are no specific, beneficial antiviral therapies for this prevalent problem. In order to develop novel therapeutic approaches for compounds with antiviral activity against papillomaviruses, we have collaborated with Dr. Elliott Androphy of the Tufts University Medical Sch, who has cloned a novel cellular protein, provisionally named 42A. This protein interacts with the papillomavirus E2 transactivation and DNA replication regulator and appears to be required for activity. We propose experiments to determine the feasibility of inhibiting the E2-42A interaction as a means of developing novel antivirals. We plan to map the domains of the proteins responsible for their interaction and then use this information to design peptides which inhibit the interaction. The peptides will be assayed in systems we have developed to measure E2-dependent regulation and for antiviral and cytotoxic activities. These Phase I studies will thus allow us to determine the feasibility of developing high throughput screens for small- molecule inhibitors of th E2-42A interaction and the likelihood that they would be of use in inhibiting papillomavirus-related pathologies.

Proposed Commercial Applications

The proposed research will establish the feasibility of disrupting the HPV E2-42A complex as a means to attain antiviral activity. Results from this work will establish whether a drug discovery program based on this approach should be established to develop novel human papillomavirus-specific antivirals.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43AI041262-01
Application #
2005791
Study Section
Special Emphasis Panel (ZRG2-SSS-4 (02))
Project Start
1997-09-15
Project End
1998-03-14
Budget Start
1997-09-15
Budget End
1998-03-14
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Signal Pharmaceuticals, LLC
Department
Type
DUNS #
City
San Diego
State
CA
Country
United States
Zip Code
92121
Kovelman, R; Bilter, G K; Roman, A et al. (1999) Human papillomavirus type 6: classification of clinical isolates and functional analysis of E2 proteins. J Gen Virol 80 ( Pt 9):2445-51