Natural small molecule compounds targeting Wnt signaling pathway inhibit HPV infection

Background: High-risk human papillomavirus (HPV) infection is a major risk factor of HPV-related tumors, especially cervical cancer. To date, there is no specific drug for the treatment of HPV infection.<br /> Purpose: To explore the role of canonical Wnt signaling pathway in HPV16 infection and to screen inhibitors against HPV16 infection from natural small molecule compounds targeting the canonicalWnt pathway.<br /> Methods: Wnt pathway inhibitor IWP-2 and FH535 were used to inhibit Wnt/(3-catenin signaling pathway. HPV16-GFP pseudovirus infectivity were analyzed by fluorescence microscopy and fluorescence activated cell sorting. A small molecule screening of a total of CFDA-approved 29 natural compounds targeting the Wnt pathway was performed.<br /> Results: Wnt signaling pathway inhibitor suppressed HPV16-GFP pseudovirus infection in HaCat cells. Natural small molecule compounds screening identified 6-Gingerol, gossypol, tanshinone II2A, and EGCG as inhibitors of HPV16-GFP pseudovirus infection.<br /> Conclusion: Wnt signaling pathway is involved in the process of HPV infection of host cells. 6-Gingerol, gossypol, tanshinone II2A, and EGCG inhibited HPV16-GFP pseudovirus infection and suppressed Wnt/(3-catenin pathway in HaCat cells.