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.
De Clercq
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Cools
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D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D043383:Adenosylhomocysteinase; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000998:Antiviral Agents; D006867:Hydrolases / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008459:Measles virus / Q000502:physiology; D012087:Reoviridae / Q000502:physiology; D014372:Tubercidin / Q000031:analogs & derivatives / Q000494:pharmacology; D014616:Vaccinia virus / Q000502:physiology; D014721:Vesicular stomatitis Indiana virus / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects*
D000903:Antibiotics, Antineoplastic; D000998:Antiviral Agents; C016391:9-(2,3-dihydroxypropyl)adenine; C031096:neplanocin A; C034072:carbocyclic 3-deazaadenosine; C045526:3-adenin-9-yl-2-hydroxypropanoic acid; D006867:Hydrolases; D043383:Adenosylhomocysteinase; D000225:Adenine; D000241:Adenosine; D014372:Tubercidin