Identification of a βCD-Based Hyper-Branched Negatively Charged Polymer as HSV-2 and RSV Inhibitor

Cyclodextrins and cyclodextrin derivatives were demonstrated to improve the antiviral potency of numerous drugs, but also to be endowed with intrinsic antiviral action. They are suitable building blocks for the synthesis of functionalized polymer structures with potential antiviral activity. Accordingly, four water-soluble hyper-branched beta cyclodextrin (beta CD)-based anionic polymers were screened against herpes simplex virus (HSV-2), respiratory syncytial virus (RSV), rotavirus (HRoV), and influenza virus (FluVA). They were characterized by FTIR-ATR, TGA, elemental analyses, zeta-potential measurements, and potentiometric titrations, while the antiviral activity was investigated with specific in vitro assays. The polymer with the highest negative charge, pyromellitic dianhydride-linked polymer (P_PMDA), showed significant antiviral action against RSV and HSV-2, by inactivating RSV free particles and by altering HSV-2 binding to the cell. The polymer fraction with the highest molecular weight showed the strongest antiviral activity and both P_PMDA and its active fractions were not toxic for cells. Our results suggest that the polymer virucidal activity against RSV can be exploited to produce new antiviral materials to counteract the virus dissemination through the air or direct contact. Additionally, the strong HSV-2 binding inhibition along with the water solubility of P_PMDA and the acyclovir complexation potential of beta CD are attractive features for developing new therapeutic topical options against genital HSV-2 infection.

Automated summary

Cyclodextrins and their derivatives have shown to enhance the antiviral potency of drugs and possess intrinsic antiviral action. In this study, water-soluble hyper-branched beta cyclodextrin-based anionic polymers were synthesized and screened for their antiviral activity against HSV-2, RSV, HRoV, and FluVA. The polymer with the highest negative charge, pyromellitic dianhydride-linked polymer (P_PMDA), exhibited significant antiviral action against RSV and HSV-2 by inactivating RSV particles and altering HSV-2 binding to cells. The results suggest that the polymer's virucidal activity against RSV could be utilized to develop new antiviral materials to counteract virus dissemination through air or direct contact.