Failure of a 3-Substituted Triazinoindole in the Prevention of Experimental Human Rhinovirus Infection

Togo, Yasushi; Schwartz, Andrew R.; Hornick, Richard B.

doi:10.1159/000221243

Cited by 20 publications

(9 citation statements)

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“…This challenge virus was previously used in a drug evaluation clinical trial (8). The fourth WI-38 cell passage of rhinovirus 32 was prepared in this laboratory from the stock culture (SF 693 strain 2nd WI-38 cell passage, kindly supplied by Vincent V. Hamparian of the Ohio State University, Columbus).…”

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confidence: 99%

“…The materials and procedures for the virus isolation from the nose and for the neutralizing antibody titrations of serum and nasal washing samples have been described elsewhere (8).…”

mentioning

confidence: 99%

“…Also studied was reduction of the infectivity titer when rhinovirus culture was maintained in the medium containing 100 jig of the drug per ml. The details of this procedure have also been described (8). In both experiments, the cell cultures received fresh medium containing the drug once a day during a 5-day test period, and all WI-38 cell tube cultures were rolled at 35 C.…”

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confidence: 99%

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Evaluation of Isoprinosine in Experimental Human Rhinovirus Infection

Pachuta

Togo

Hornick

et al. 1974

Antimicrob Agents Chemother

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The prophylactic efficacy of isoprinosine was evaluated in a doubleblind fashion in volunteers challenged with two types of rhinovirus. In the rhinovirus 44 and 32 trials, each of 9 men received a placebo, and eight and 11 men received the drug, respectively. Oral isoprinosine, 6 g a day, was given for 2 days prior to intranasal challenge with 100 mean tissue culture infective doses of the virus and for 7 postchallenge days. In both trials the occurrence and severity of colds were greater in the placebo group, but the difference between the two groups was not significant. Higher antibody titers for both viruses and a greater number of rhinovirus 32 isolations were demonstrated in the drug group but without statistically significant differences. The prophylactic isoprinosine treatment may suppress the cold syndrome, but its effect was not convincingly apparent.Isoprinosine (NPT 10381, p-acetamidobenzoic acid salt of inosine-dimethylaminoisopropanol in a 1:3 [vol/vol] 403rhinovirus 44 was used as the challenge virus. This challenge virus was previously used in a drug evaluation clinical trial (8). The fourth WI-38 cell passage of rhinovirus 32 was prepared in this laboratory from the stock culture (SF 693 strain 2nd WI-38 cell passage, kindly supplied by Vincent V. Hamparian of the Ohio State University, Columbus). The examination of these challenge pools revealed no contaminants.Drug administration and viral challenge. Volunteers received orally either 1.5 g of isoprinosine at each meal and bedtime (6 g per day) or placebo tablets for 2 days prior to the intranasal inoculation of 100 TCID,5 of the challenge virus and for 7 consecutive postchallenge days. The drug and placebo tablets were supplied in coded bottles by Newport Pharmaceutical International, Inc., Newport Beach, Calif., and administered to volunteers in a double-blind fashion. A baseline observation period of 4 days was maintained to rule out incipient viral infection, and subsequently all subjects were kept in an isolation ward for 10 days after the challenge. Each subject was interviewed and examined by the physician once a day. Signs and symptoms of cold, i.e., rhinitis, rhinorrhea, nasal stuffiness, sore throat, pharyngitis, sneezing, cough, and others, were individually scored on a scale of 0 to 3+: 0, not present; 1+, mild; 2+, moderate; and 3+, severe. Each patient's chart was reviewed after discharge from the isolation ward, and the severity of induced rhinovirus illness of each subject was rated from 0 to 3+, according to the occurrence and severity of signs and symptoms and the duration of the illness. Hemogram, blood chemistries, including plasma and urine uric acid levels, and urinalysis were performed before, during, and after the isoprinosine treatment. The chest roentgenograms were done during the baseline period and before discharge from the ward.

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confidence: 99%

“…The materials and procedures for the virus isolation from the nose and for the neutralizing antibody titrations of serum and nasal washing samples have been described elsewhere (8).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

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Evaluation of Isoprinosine in Experimental Human Rhinovirus Infection

Pachuta

Togo

Hornick

et al. 1974

Antimicrob Agents Chemother

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“…The materials and procedures for the virus isolation from the nose and for the neutralizing antibody titrations of serum and nasal washing samples have been described elsewhere (9).…”

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confidence: 99%

“…The reduction of the infectivity titer of the rhinovirus which was cultured with the medium containing 100 1g/ml of DIQA was also studied. The details of this procedure have also been described (9). In order to determine the direct activity of DIQA on the rhinoviruses, the drug solution and each of the viruses were mixed together to make the drug concentration in the mixture 1,000 AgIml.…”

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confidence: 99%

Antiviral Effect of 3,4-Dihydro-1-Isoquinolineacetamide Hydrochloride in Experimental Human Rhinovirus Infection

Togo

Schwartz

Hornick

1973

Antimicrob Agents Chemother

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Double-blind trials were conducted in volunteers to evaluate the efficacy of the prophylactic 3,4-dihydro-1-isoquinolineacetamide hydrochloride (DIQA) treatment against rhinovirus type 24 challenge. Ten men received a 7-day course of DIQA treatment and 11 men received a placebo. The intranasal viral challenge dose was 10 mean tissue culture infective doses. The oral administration of 1 g prechallenge and 2 g a day for 6 consecutive postchallenge days did not prevent the development of colds. Nine drug-treated men and 10 controls developed rhinovirus illness. However, the illnesses of the drug-treated men were mild. Rhinorrhea occurred less frequently and was more mild in the drug-treated group. The challenge virus was recovered from 80% of these subjects in both groups, but almost twice the number of challenge viruses were isolated from the controls than from the drug-treated men. The prophylactic DIQA therapy appears to suppress the cold syndrome and to reduce virus excretion, although its effect is marginal. Additional clinical trials are warranted to confirm the antirhinoviral effect of this drug.An antiviral compound, 3, 4-dihydro-1-isoquinolineacetamide hydrochloride (DIQA; Fig. 1) has been shown to be prophylactically effective in mice against infections produced by influenza (A/PR/8/34 and A/Japan/305/57), ECHO 9 (Coxsackie A23), herpes simplex, encephalomyocarditis (Columbia SK), St. Louis encephalitis, and West Nile viruses. The drug exhibited prophylactic and therapeutic activity against mumps infection in monkeys and effectively suppressed the development of herpes keratitis in rabbits, but the drug did not exert any effect on these viruses in tissue cultures.DIQA was active against Coxsackievirus Bi and vaccinia in tissue cultures, but was ineffective in vivo (1-3, 6).Two isoquinoline derivatives (UK 2054 and UK 2371) inhibited the in vitro growth of viruses belonging to the myxovirus and picornavirus groups (4). In experimentally induced ' Present address: Division of Infectious Diseases, Department of Medicine, Hahnemann Medical College & Hospital of Philadelphia, Philadelphia, Pa. 19102. types A and B influenza in man, the prophylactic treatment by UK 2371 (7) and by UK 2054 (5) significantly reduced the occurrence of the illness and suppressed the signs and symptoms. UK 2054, which showed an in vitro inhibitory action on rhinovirus type 9, failed to prevent experimental human infection of this virus (8).Although

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Rhinoviruses

Gwaltney

1989

Viral Infections of Humans

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Failure of a 3-Substituted Triazinoindole in the Prevention of Experimental Human Rhinovirus Infection

Cited by 20 publications

References 5 publications

Evaluation of Isoprinosine in Experimental Human Rhinovirus Infection

Evaluation of Isoprinosine in Experimental Human Rhinovirus Infection

Antiviral Effect of 3,4-Dihydro-1-Isoquinolineacetamide Hydrochloride in Experimental Human Rhinovirus Infection

Rhinoviruses

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