In vivo efficacy of SDZ 35-682, a new picornavirus capsid-binding agent

SDZ 35-682 is a potent and selective inhibitor of the replication of members of the picornavirus group. It belongs to the group of uncoating inhibitors binding to the hydrophobic pocket in the capsid of the virion. In cell culture it inhibits several rhinovirus serotypes and echovirus 9 at concentrations as low as 0.1 micrograms/ml. In the echovirus 9 animal model the protective effect of SDZ 35-682 was found to be dependent on both, dose of drug and duration of treatment. Significant protection of newborn mice from paralysis and death could be achieved by either a high dose (126 mg/kg) given only twice, at days 0 and 1 relative to echovirus 9 inoculation, or by a lower dose administered for 4 or 6 days. This finding might be explained by assuming a long half-life for SDZ 35-682. Though clinical usefulness of SDZ 35-682 may be limited by its relatively narrow antiviral spectrum it represents a novel potent and selective inhibitor of rhinovirus and echovirus 9 replication in cell culture and in the organism.