Failure of oral 4′, 6-dichloroflavan to protect against rhinovirus infection in man

Abstract

4',6-Dichloroflavan, a potent inhibitor of rhinovirus replication in vitro, was tested in a double-blind placebo controlled volunteer trial for its protective effect against experimental rhinovirus infection. Dichloroflavan was given orally (1 mg/kg, 3 times per day) for 3 doses before, and 13 doses after intranasal challenge with rhinovirus type 9, a type known to be highly sensitive in tissue culture. A total of 63 volunteers were included in the analysis for efficacy. Dichloroflavan did not produce any consistent or significant reduction in quantitative clinical or laboratory evidence of infection, and there was no apparent negative correlation of such data with drug concentrations in plasma. It is concluded that administration of dichloroflavan in the oral formulation tested is not of value in the treatment of human rhinovirus infection.

Antirhinovirus activity of purine nucleoside analogs

“…No significant effects on rhinorrhea, clinical score, or virus excretion were noted whether the compounds were given intranasally (21,26,28,33,43) or orally (32,40 The fine editorial assistance of Christiane Callebaut is gratefully acknowledged.…”

“…Despite their potent and selective antiviral activity in vitro, the rhinovirus inhibitors that have so far been the subject of clinical studies, viz., enviroxime (21,26,28,33), 4',6-dichloroflavan (32), and some isoquinoline derivatives (40,43), have proven of little, if any, value in the prophylaxis or therapy of rhinovirus infections in volunteers. No significant effects on rhinorrhea, clinical score, or virus excretion were noted whether the compounds were given intranasally (21,26,28,33,43) or orally (32,40 The fine editorial assistance of Christiane Callebaut is gratefully acknowledged.…”

“…The search for effective antirhinovirus agents has yielded a wealth of compounds belonging to widely varying chemical classes: thiosemicarbazones (20), isoquinolines (35,43), triazinoindoles (27), guanidines (5), benzoates (30), furanyls (2), benzimidazoles (12), thiourea (18), diketones (14,16,17), flavans (3,32), flavones (25), chalcones (24), nitrobenzenes (34,41), and isoxazoles (15,31). The most recently developed antirhinovirus compounds (3,15,24,31) reach their MICs within the range of 0.001 to 0.01 ,ug/ml.…”

Intranasal interferon as protection against experimental respiratory coronavirus infection in volunteers

“…Volunteers were matched for age and sex and were assigned to receive either interferon or placebo in such a way that only one preparation was used in any one flat. After a 2-day quarantine period, the volunteers administered interferon or placebo to themselves, intranasally, three times a day for 4 days by a finger-actuated spray (Mistette Mark 11, kindly supplied by Calmar-Albert, GmbH, Hemer, Federal Republic of Germany). Each medication, two sprays of approximately 0.1 ml each to each nostril, was supervised by a member of the staff.…”

Safety and efficacy of intranasal pirodavir (R77975) in experimental rhinovirus infection

“…These agents appear to bind into a specific hydrophobic pocket within the capsid protein VP1, beneath the canyon floor of rhinoviruses, and prevent viral attachment and/or uncoating, depending on the serotype involved (13,15). However, clinical trials in which several of the agents were administered orally or intranasally yielded negative results (2,3,14,18). The first of these agents to show clinical activity in studies with humans was the pyridazinamine R61837 (1,7).…”