Antiviral Activity of 4′-thioIDU and Thymidine Analogs against Orthopoxviruses

The search for effective therapies for orthopoxvirus infections has identified diverse classes of molecules with antiviral activity. Pyrimidine analogs, such as 5-iodo-2'-deoxyuridine (idoxuridine, IDU) were among the first compounds identified with antiviral activity against a number of orthopoxviruses and have been reported to be active both in vitro and in animal models of infection. More recently, additional analogs have been reported to have improved antiviral activity against orthopoxviruses including several derivatives of deoxyuridine with large substituents in the 5 position, as well as analogs with modifications in the deoxyribose moiety including (north)-methanocarbathymidine, and 5-iodo-4'-thio-2'-deoxyuridine (4'-thioIDU). The latter molecule has proven to have good antiviral activity against the orthopoxviruses both in vitro and in vivo and has the potential to be an effective therapy in humans.