Antiviral activity of gemcitabine against human rhinovirus in?vitro and in?vivo

摘要

Abstract 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. Highlights ? Gemcitabine, 2′,2′-difluorodeoxycytidine, has antiviral activity against rhinovirus in?vitro. ? The antirhinoviral activity of gemcitabine may be mediated by decreasing levels of NTP. ? Intranasal administration of gemcitabine blocked rhinovirus infection in murine model of HRV1B infection in?vivo.