| Popis: |
Infection with human papillomavirus (HPV) represents a complex presentation of symptoms, from benign warts to cancer. Prevention options for sexually active individuals outside the nonavalent HPV vaccine range are limited. Thus, the overarching aim of this dissertation work was to prevent HPV at the cellular level by investigating FDA- and internationally-approved drugs with the potential to prevent HPV infection. To this end, I conducted three research studies: a) a review of the literature focusing on human papillomavirus (HPV) biology, pathogenesis, and potential for drug discovery; b) developed a HPV-16 cell based assay for high-throughput screening (HTS) to conduct a pilot screen of 1906 compounds the Small Molecule Discovery Center at UCSF, and c) performed dose-response activity confirmation and investigated mechanisms of action for top candidate drugs. The results of these three studies demonstrate that the identification of novel anti-HPV drugs to be used for HPV prevention in the sexually active population is linked to understanding HPV biology; and using a HTS HPV-16 cell based assay is a valid and reliable tool for identifying potential anti-HPV to prevent HPV infection. Overall, my goal was to identify previously approved FDA- and internationally-approved drugs that have the potential to be repurposed for HPV prevention in sexually active individuals outside the of nonavalent vaccination range. |
