Disodium phosphonoacetate when administered orally or topically to mice experimentally infected with herpes simplex virus was able to significantly reduce the mortality associated with the agent. In addition, this compound was able to reduce herpesvirus lesions on the corneas of infected rabbits.

The marked antiviral activity of (S,S-1,2-bis(5-methoxy-2-benzimidazolyl)-1, 2-ethanediol (Abbott 36683) against rhinoviruses in tissue culture warranted investigation of its antiviral activity in vivo. Antiviral levels in mouse sera were attained with an oral dose as small as 10 mg/kg and detectable antiviral levels of drug were also found in lung, liver, kidney, intestinal contents, and urine of mice given a single 300 mg/kg oral dose. Antiviral serum levels were also obtained when monkeys were given a single oral dose of Abbott 36683. Six chimpanzees were infected with 100 median tissue culture infective dose units (TCID50) of rhinovirus 30. Three of the animals were treated with Abbott 36683, 100 mg/kg daily for 4 consecutive days. Virus shedding occurred in the infected controls but could not be demonstrated in the treated animals from postinfection days 1 to 8. Two of the treated animals did, however, shed virus on day 9. The compound was retested in chimpanzees at dosage levels of 15 and 50 mg/kg daily for 4 days. Each animal was challenged with 100 TCIDO of rhinovirus 49. Partial protection was obtained. In a third trial, a single 100 mg/kg dose of the compound was administered to chimpanzees infected with rhinovirus 44. Virus was isolated from all throat smears taken from treated animals, indicating that at the lowest drug level no protection occurred.

The marked antiviral activity of ( S,S -1,2-bis(5-methoxy-2-benzimidazolyl)-1,2-ethanediol (Abbott 36683) against rhinoviruses in tissue culture warranted investigation of its antiviral activity in vivo. Antiviral levels in mouse sera were attained with an oral dose as small as 10 mg/kg and detectable antiviral levels of drug were also found in lung, liver, kidney, intestinal contents, and urine of mice given a single 300 mg/kg oral dose. Antiviral serum levels were also obtained when monkeys were given a single oral dose of Abbott 36683. Six chimpanzees were infected with 100 median tissue culture infective dose units (TCID 50 ) of rhinovirus 30. Three of the animals were treated with Abbott 36683, 100 mg/kg daily for 4 consecutive days. Virus shedding occurred in the infected controls but could not be demonstrated in the treated animals from postinfection days 1 to 8. Two of the treated animals did, however, shed virus on day 9. The compound was retested in chimpanzees at dosage levels of 15 and 50 mg/kg daily for 4 days. Each animal was challenged with 100 TCID 50 of rhinovirus 49. Partial protection was obtained. In a third trial, a single 100 mg/kg dose of the compound was administered to chimpanzees infected with rhinovirus 44. Virus was isolated from all throat smears taken from treated animals, indicating that at the lowest drug level no protection occurred.

( S,S )-1,2-bis(5-methoxy-2-benzimidazolyl)-1,2-ethanediol showed antiviral activity in monolayer tissue culture systems against 55 strains of rhinovirus, three types of poliovirus, and strains of type A and B coxsackieviruses. Neither the compound nor any of the analogues tested showed virucidal activity. Its antiviral activity was not associated with interference with viral attachment to or penetration into the cell. At a concentration of 0.1 mg/ml, this group of compounds was generally nontoxic to WI-38, primary bovine kidney, and African green monkey kidney cells and had antiviral activity with 100% inhibition of virus-induced cytopathic effects (CPE). At antiviral levels, these compounds prevented CPE of up to 10 6 median tissue culture infective dose units of virus and completely inhibited formation of new infective virions. The compounds showed antiviral activity both prophylactically and therapeutically against rhinoviruses. Infected cultures could be cleared of CPE up to 90 hr after infection.