Laboratory of Molecular Virology and Antiviral Research, Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, Orbassano, 10043 Turin, Italy.
Department of Chemistry, NIS Interdepartmental Centre, University of Turin, Via P. Giuria 7, 10125 Turin, Italy.
Int J Mol Sci. 2022 Aug 4;23(15):8701. doi: 10.3390/ijms23158701.
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 (βCD)-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 βCD are attractive features for developing new therapeutic topical options against genital HSV-2 infection.
环糊精及其衍生物被证明可以提高许多药物的抗病毒效力，同时也具有内在的抗病毒作用。它们是合成具有潜在抗病毒活性的功能化聚合物结构的合适构建块。因此，我们筛选了四种水溶性超支化β环糊精（βCD）基阴离子聚合物，以对抗单纯疱疹病毒（HSV-2）、呼吸道合胞病毒（RSV）、轮状病毒（HRoV）和流感病毒（FluVA）。它们的结构通过傅里叶变换衰减全反射（FTIR-ATR）、热重分析（TGA）、元素分析、动电位测量和电位滴定进行了表征，而抗病毒活性则通过特定的体外测定进行了研究。带负电荷最高的聚合物，均苯四酸二酐连接聚合物（P_PMDA），对 RSV 和 HSV-2 具有显著的抗病毒作用，通过使 RSV 游离颗粒失活以及改变 HSV-2 与细胞的结合来实现。分子量最高的聚合物部分显示出最强的抗病毒活性，而且 P_PMDA 及其活性部分对细胞没有毒性。我们的结果表明，该聚合物对 RSV 的病毒杀灭活性可用于开发新的抗病毒材料，以阻止病毒通过空气或直接接触传播。此外，P_PMDA 的高水溶性、与阿昔洛韦的络合潜力以及对 HSV-2 的强结合抑制作用，为开发针对生殖器 HSV-2 感染的新型局部治疗选择提供了有吸引力的特征。
