Antiviral activity of gemcitabine against human rhinovirus in vitro and in vivo.
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.
['Song|Jae-Hyoung|JH|', 'Kim|Seong-Ryeol|SR|', 'Heo|Eun-Young|EY|', 'Lee|Jae-Young|JY|', 'Kim|Dong-Eun|DE|', 'Cho|Sungchan|S|', 'Chang|Sun-Young|SY|', 'Yoon|Byung-Il|BI|', 'Seong|Jeongmin|J|', 'Ko|Hyun-Jeong|HJ|']
D000818:Animals D000998:Antiviral Agents D016207:Cytokines D003841:Deoxycytidine D004195:Disease Models, Animal D058492:Drug Repositioning D006801:Humans D007249:Inflammation D008168:Lung D051379:Mice D010850:Picornaviridae Infections D012367:RNA, Viral D012229:Rhinovirus D019562:Viral Load D014779:Virus Replication
Gemcitabine Rhinovirus Inflammation Proinflammatory cytokines Antiviral drug