Compositions and methods for treating human papilloma virus infections
The invention provides compositions, compounds, formulations, and methods for treating HPV infections including pre-malignant infections and cancer. Compounds that covalently bind to the HPV E6 protein are disclosed.
1. A compound that forms a covalent bond with a Cysteine residue in the E6AP binding pocket of a human papillomavirus E6 protein, thereby preventing interaction of the HPV E6 protein with an E6AP protein.
2. The compound of claim 1 , wherein said compound binds to Cysteine 51 in the HPV-16 E6 protein.
3. The compound of claim 1 , wherein said compound contains an acrylamide that forms a covalent bond to a Cysteine in the E6AP binding pocket of a human papillomavirus E6 protein.
4. A formulation comprising the compound of claim 1 .
5. The formulation of claim 4 , comprising a pharmaceutically acceptable adjuvant, diluent or earner.
6. The formulation of claim 4 , provided in a nanoparticle for targeted delivery.
7. A method for treating an HPV infection, dysplasia, or malignancy, the method comprising the step of delivering a formulation according to claim 5 .
8. The method of claim 7 , wherein said formulation is delivered orally, transdermally, topically, subcutaneously, intramuscularly, intralesionally or intravenously.
9. The method of claim 7 , wherein the formulation is formulated for topical application to the cervix, anus, or pharynx.
10. The method of claim 8 , wherein said formulation comprises an effective dose for transdermal delivery of about 0.01% to about 10% of the compound of claim 1 .
11. The method of claim 8 , wherein said formulation is a time-release formulation.
12. The method of claim 7 , wherein said formulation inhibits E6AP binding to HPV E6 preventing ubiquitination of p53.
13. The formulation of claim 5 , wherein the formulation further comprises a compound selected from the group consisting of fatty acids, glucose, amino acids, cholesterol, lipids, glycosides, alkaloids, and natural phenols.