کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2509847 | 1557831 | 2014 | 9 صفحه PDF | دانلود رایگان |
• A permissive animal model was used to test the efficacy of three drugs against disseminated human adenovirus infection.
• These three drugs are used in the clinic to treat disseminated adenovirus infection in immunocompromised patients.
• Two of the three drugs, cidofovir and brincidofovir, were very efficacious in the model.
• Ribavirin had no significant anti-adenoviral activity in our model.
• The virtues of the immunosuppressed Syrian hamster model are discussed.
There are no drugs approved specifically to treat disseminated adenovirus (Ad) infections in humans. Cidofovir is active against Ad in cell culture, and it is used frequently in the clinic with disseminated infection in pediatric transplant patients; however, controlled clinical studies have not been conducted to prove the anti-Ad efficacy of cidofovir. Brincidofovir, a lipid-linked derivative of cidofovir, which has strong activity against Ad in cell culture and in animal models, is a promising new drug currently in clinical trials. Ribavirin, which has modest activity against some Ad types in cell culture, has been used in the clinic against disseminated Ad, but the efficacy of ribavirin is unknown. In the current study, we have examined the activity of cidofovir, brincidofovir, and ribavirin against disseminated Ad5 infection in the immunosuppressed Syrian hamster model. Hamsters are immunosuppressed by treatment with cyclophosphamide, then infected intravenously with Ad5, leading to disseminated Ad5 infection, especially in the liver. We found that cidofovir and brincidofovir have excellent activity against Ad5 pathology and replication in the liver, even when administered therapeutically starting at 3 days post-challenge with Ad5. Ribavirin did not have anti-Ad5 activity in our model. Our data support the use of cidofovir and brincidofovir in humans for the treatment of disseminated Ad infections in humans.
Journal: Antiviral Research - Volume 112, December 2014, Pages 38–46