Rhinovirus, a major causative agent of the common cold, is associated with exacerbation of asthma and chronic obstructive pulmonary disease. Currently, there is no antiviral treatment or vaccine for human rhinovirus (HRV). Gemcitabine (2′,2′-difluorodeoxycytidine, dFdC) is a deoxycytidine analog with antiviral activity against rhinovirus, as well as enterovirus 71, in vitro. However, the antiviral effects of gemcitabine in vivo have not been investigated. In the current study, we assessed whether gemcitabine mediated antiviral effects in the murine HRV infection model. Intranasal administration of gemcitabine significantly lowered pulmonary viral load and inflammation by decreasing proinflammatory cytokines, including TNF-α and IL-1β, and reduction in the number of lung-infiltrating lymphocytes. Interestingly, we found that the addition of UTP and CTP significantly attenuated the antiviral activity of gemcitabine. Thus the limitation of UTP and CTP by the addition of gemcitabine may inhibit the viral RNA synthesis. These results suggest that gemcitabine, an antineoplastic drug, can be repositioned as an antiviral drug to inhibit HRV infection.

鼻病毒是普通感冒的主要病因，它与哮喘加重和慢性阻塞性肺疾病有关。当前，尚无针对人类鼻病毒（HRV）的抗病毒治疗或疫苗。吉西他滨（2'，2'-二氟脱氧胞苷，dFdC）是一种脱氧胞苷类似物，在体外对鼻病毒和肠病毒71具有抗病毒活性。然而，尚未研究吉西他滨在体内的抗病毒作用。在当前的研究中，我们评估了吉西他滨在小鼠HRV感染模型中是否介导了抗病毒作用。鼻内给药吉西他滨可通过减少促炎细胞因子（包括TNF-α和IL-1β）并减少肺部浸润淋巴细胞的数量来显着降低肺部病毒载量和炎症。有趣的是，我们发现，添加UTP和CTP可以显着减弱吉西他滨的抗病毒活性。因此，通过加入吉西他滨来限制UTP和CTP可能会抑制病毒RNA的合成。这些结果表明，抗肿瘤药吉西他滨可以重新定位为抑制HRV感染的抗病毒药物。