The inhibitory effects and mechanisms of 3,6-O-sulfated chitosan against human papillomavirus infection.

High-risk human papillomavirus (HPV) infection can lead to the development of cervical cancers that are a significant health burden worldwide. The heparin-like polysaccharides such as dextran sulfate and carrageenan were reported to be able to prevent the binding of HPV to the cell surface. In this study, a 3,6-O-sulfated chitosan (36S) was prepared, and its anti-HPV effects were explored. The results showed that 36S effectively inhibited multiple genital HPV genotypes in different cell lines with low cytotoxicity. 36S may possibly block HPV adsorption via direct binding to the viral capsid proteins. 36S could enter into Hela cells and down-regulate cellular PI3K/Akt/mTOR pathway which is associated with autophagy. Thus, marine derived sulfated chitosan 36S possessed broad anti-HPV activities in vitro, and may possibly inhibit HPV infection by targeting viral capsid protein and host PI3K/Akt/mTOR pathway, suggesting that 36S merits further investigation as a novel anti-HPV agent.