Antiviral potency of adenosine analogues: correlation with inhibition of S-adenosylhomocysteine hydrolase.

For a series of adenosine analogues a close correlation (r = 0.986) was found between their antiviral potency (against vesicular stomatitis virus) and their inhibitory effects (Ki/Km) on S-adenosylhomocysteine (AdoHcy) hydrolase; thus, in order of increasing inhibitory potency for both virus replication and AdoHcy hydrolase activity: (S)-9-(2,3-dihydroxypropyl)adenine less than (RS)-3-adenin-9-yl-2-hydroxypropanoic acid (isobutyl ester) less than carbocyclic 3-deazaadenosine less than neplanocin A. Our findings point to AdoHcy hydrolase as the target for the broad-spectrum antiviral activity of these adenosine analogues.