Comparative efficacy of broad-spectrum antiviral agents as inhibitors of rotavirus replication in vitro.
Several nucleoside analogues which have previously been established as broad-spectrum antiviral agents, i.e. ribavirin, vidarabine, pyrazofurin, tubercidin, carbodine, (S)-9-(2,3-dihydroxypropyl)adenine [(S)-DHPA], carbocyclic 3-deazaadenosine (C-c3 Ado), (RS)-3-adenine-9-yl-2-hydroxypropanoic acid [(RS)-AHPA] isobutyl ester and neplanocin A were compared for their potency and selectivity as inhibitors of human rotavirus (strains Wa, KUN and MO) replication in vitro. As the most efficacious inhibitors emerged (S)-DHPA, C-c3 Ado, (RS)-AHPA isobutyl ester and neplanocin A, with a minimum inhibitory concentration of 60, 1.4, 1.2 and 0.2 micrograms/ml, and a selectivity index of greater than 3, 70, 80 and greater than 20, respectively. As has been postulated for their antiviral action in general, these adenosine analogues probably owe their anti-rotavirus activity to inhibition of S-adenosylhomocysteine hydrolase, a key enzyme in regulating methylations including those that are required for the maturation of viral mRNA.
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000577:Amides; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D003562:Cytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D011720:Pyrazoles; D012254:Ribavirin / Q000494:pharmacology; D012263:Ribonucleosides / Q000494:pharmacology; D012266:Ribose; D012401:Rotavirus / Q000187:drug effects*; D014372:Tubercidin / Q000031:analogs & derivatives / Q000494:pharmacology; D014740:Vidarabine / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
D000577:Amides; D000998:Antiviral Agents; D011720:Pyrazoles; D012263:Ribonucleosides; D012254:Ribavirin; C002997:pyrazofurin; C016391:9-(2,3-dihydroxypropyl)adenine; D003562:Cytidine; D012266:Ribose; C033357:carbodine; C031096:neplanocin A; C034072:carbocyclic 3-deazaadenosine; C048336:3-adenin-9-yl-2-hydroxypropanoic acid isobutyl ester; D014740:Vidarabine; D000225:Adenine; D000241:Adenosine; D014372:Tubercidin