The picornavirus replication inhibitors HBB and guanidine in the echovirus-9 system: the significance of viral protein 2C

HBB [2-(alpha-hydroxybenzyl)-benzimidazole] and guanidine are potent inhibi tors of picornavirus replication. Among other evidence, limited cross-resis tance and a synergistic effect of both inhibitors suggest similar but not i dentical mechanisms of antiviral action. Echovirus-9 variants resistant to each of these drugs were characterized and sequenced. Complete resistance t o HBB or guanidine was shown to be due to single but different point mutati ons in the non-structural protein 2C. Protein 2C was expressed as GST fusio n and His-tagged proteins for the wild-type and various mutants. Although t hree mutations were located in or near conserved NTP binding motifs, NTPase activity was not altered in the presence of HBB or guanidine.