Small Molecule Inhibitors of Human Papillomavirus Protein - Protein Interactions



C.M D’Abramo, J Archambault*
Laboratory of Molecular Virology, Institut de Recherches Cliniques de Montréal and Department of Biochemistry, Université de Montréal, Montreal, Quebec, Canada


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© D’Abramo and Archambault; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http: //creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Laboratory of Molecular Virology, Institut de Recherches Cliniques de Montréal, 110 Pine Avenue West, Montreal, Quebec, H2W 1R7, Canada; Tel: (514) 987-5739; Fax: (514) 987-5741; E-mail: jacques.archambault@ircm.qc.ca


Abstract

Human papillomaviruses (HPV) have now been identified as a necessary cause of benign and malignant lesions of the differentiating epithelium, particularly cervical cancer, the second most prevalent cancer in women worldwide. While two prophylactic HPV vaccines and screening programs are available, there is currently no antiviral drug for the treatment of HPV infections and associated diseases. The recent progress toward the identification and characterization of specific molecular targets for small molecule-based approaches provides prospect for the development of effective HPV antiviral compounds. Traditionally, antiviral therapies target viral enzymes. HPV encode for few proteins, however, and rely extensively on the infected cell for completion of their life cycle. This article will review the functions of the viral E1 helicase, which encodes the only enzymatic function of the virus, of the E2 regulatory protein, and of the viral E6 and E7 oncogenes in viral replication and pathogenesis. Particular emphasis will be placed on the recent progress made towards the development of novel small molecule inhibitors that specifically target and inhibit the functions of these viral proteins, as well as their interactions with other viral and/or cellular proteins.

Keywords: HPV, cervical cancer, protein interaction, small molecule inhibitor, E1, E2, E6, E6AP..