Icosagen has identified 5 compounds that inhibit HPV18 genome amplification in low micromolar range
Icosagen has developed a specific 3D cell-based assay to identify human papillomavirus (HPV) DNA replication inhibitors in high-throughput format. In a proof of concept (PoC) study, 5 high-risk HPV specific inhibitors were identified.
None of the identified compounds inhibit E1 and E2 dependent URR replication. Besides viral genome amplification, four out of five compounds successfully inhibited the stable maintenance phase of the viral replication. In addition, three compounds inhibited vegetative amplification of the viral genome, which takes place in highly differentiated upper epithelia.
These inhibitors or their analogues are therefore capable of eliminating different stages of HPV infection. The identified compounds do not inhibit E1 and E2 independent URR replication, indicating that different cellular protein could be used to facilitate HPV genome replication and/or that the replication mechanism of viral genome differs from the URR plasmid replication.
Mechanism of action
Patents
1. Title: Human papilloma virus replication inhibitors
International Application No. PCT/EP2016/060584
Scientific publication
1 Toots M, et al. (2017) Identification of several high-risk HPV inhibitors and drug targets with a novel high-throughput screening assay. PLoS Pathog 13(2): e1006168.