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-adenin-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 μg/ml, and a selectivity index of >3, 70, 80 and >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.