Broad-spectrum antiviral activity of adenosine analogues

In recent years certain aliphatic and carbocyclic adenosine analogues have been developed which are of potential clinical importance as antiviral agents. This includes (S)-9-(2,3-dihydroxypropyl)adenine [(S)-DHPA] and carbocyclic 3-deazaadenosine (C-c3Ado). (S)-DHPA and C-c3Ado are remarkably similar in their antiviral spectrum in that they are particularly active against (-) RNA viruses such as measles, para-influenza, respiratory syncytial virus, rabies virus, vesicular stomatitis virus and (+/-)RNA viruses such as reo- and rotavirus, whereas (+)RNA viruses such as polio, coxsackie and (+/-)DNA viruses such as herpes simplex are only minimally affected or not inhibited at all. In contrast with (S)-DHPA and C-c3Ado which are quite selective in their antiviral action, other adenosine analogues, i.e., 3-deazaadenosine and 7-deazaadenosine (tubercidin), exhibit little, if any, selectivity as antiviral agents. Also, tubercidin has a broader activity spectrum, encompassing (+)RNA viruses as well as herpes simplex in addition to the (-)RNA viruses. Considering the high antiviral potency of tubercidin, attempts have been undertaken to increase its selectivity, i.e., by chemical substitutions at C-5 of the pyrrolo(2,3-d)pyrimidine ring. These attempts have been partially successful.