Mastrangelo Peter, Norris Michael J, Duan Wenming, Barrett Edward G, Moraes Theo J, Hegele Richard G
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Department of Paediatrics, The Hospital for Sick Children, Toronto, ON M5G 1L5, Canada.
Vaccines (Basel). 2017 Sep 19;5(3):27. doi: 10.3390/vaccines5030027.
Nucleolin (NCL) has been reported as a cellular receptor for the human respiratory syncytial virus (RSV). We studied the effects of re-purposing AS1411, an anti-cancer compound that binds cell surface NCL, as a possible novel strategy for RSV therapy in vitro and in vivo. AS1411 was administered to RSV-infected cultures of non-polarized (HEp-2) and polarized (MDCK) epithelial cells and to virus-infected mice and cotton rats. Results of in vitro experiments showed that AS1411, used in micromolar concentrations, was associated with decreases in the number of virus-positive cells. Intranasal administration of AS1411 (50 mg/kg) to RSV-infected mice and cotton rats was associated with partial reductions in lung viral titers, decreased virus-associated airway inflammation, and decreased IL-4/IFN-γ ratios when compared to untreated, infected animals. In conclusion, our findings indicate that therapeutic use of AS1411 has modest effects on RSV replication and host response. While the results underscore the challenges of targeting cell surface NCL as a potential novel strategy for RSV therapy, they also highlight the potential of cell surface NCL as a therapeutic target.
核仁素（NCL）已被报道为人类呼吸道合胞病毒（RSV）的细胞受体。我们研究了重新利用AS1411（一种与细胞表面NCL结合的抗癌化合物）作为RSV治疗的一种可能新策略在体外和体内的效果。将AS1411施用于未极化（HEp-2）和极化（MDCK）上皮细胞的RSV感染培养物以及病毒感染的小鼠和棉鼠。体外实验结果表明，微摩尔浓度使用的AS1411与病毒阳性细胞数量的减少有关。与未治疗的感染动物相比，对RSV感染的小鼠和棉鼠鼻内施用AS1411（50mg/kg）与肺病毒滴度的部分降低、病毒相关气道炎症的减轻以及IL-4/IFN-γ比值的降低有关。总之，我们的研究结果表明，AS1411的治疗应用对RSV复制和宿主反应有适度影响。虽然结果强调了将细胞表面NCL作为RSV治疗潜在新策略的挑战，但它们也突出了细胞表面NCL作为治疗靶点的潜力。
