ABSTRACT
WIN 51711 (5-[7-[4-(4,5-dihydro-2-oxazolyl)phenoxy]heptyl]-3-methylisoxazole), a new antipicornavirus drug, is a potent inhibitor of human entero- and rhinoviruses at concentrations not inhibitory to HeLa cell growth. In plaque reduction assays, WIN 51711 reduced plaque formation by 9 enteroviruses and 33 rhinoviruses, with MICs of 0.004 to 0.17 and 0.004 to 6.2 micrograms/ml, respectively. Addition of WIN 51711 to infected cells at concentrations of 0.02 to 5.0 micrograms/ml reduced the yield of picornaviruses by 90%. Other RNA viruses (nonpicornaviruses) and DNA viruses were unaffected by the compound.
Subject(s)
Antiviral Agents/pharmacology , Isoxazoles/pharmacology , Oxazoles/pharmacology , Picornaviridae/drug effects , Culture Media , Enterovirus/drug effects , HeLa Cells , Humans , Rhinovirus/drug effects , Time Factors , Viral Plaque Assay , Virus Replication/drug effectsABSTRACT
Rhinoviruses as a group are notably sensitive to inactivation in solutions with a pH of less than 5.3. Glutaric acid appears to possess virucidal activity in addition to the aciduant effect against rhinoviruses. A model system in which rhinovirus type 14 was incubated in the presence of glutaric acid (GA) (pH 4.0) at 0 degrees C was devised to separate intrinsic virucidal activity from the aciduant effect. Under these conditions, virucidal activity against rhinovirus type 14 was directly related to the concentration of GA present and the proportion of the acid in the diprotonated form. The virucidal activities of GA and several other compounds, including GA analogs and other mono- and dicarboxylic acids, were tested under the conditions described. In general, as the alkane bridge separating two carboxylic acid functions was lengthened, virucidal activity decreased. When 26 additional strains of rhinoviruses were tested in the model system, 19 were inactivated slowly enough to be compared. Of these, 63% were more susceptible to GA than to sodium acetate buffer and 26% were more susceptible to sodium acetate buffer. Eleven percent were resistant to both GA and sodium acetate buffer. The virucidal activity of GA for a majority of strains tested appeared to be due to combination of low pH and another mechanism of action presumably unrelated to pH.
Subject(s)
Antiviral Agents/pharmacology , Glutarates/pharmacology , Rhinovirus/drug effects , Cold Temperature , Drug Resistance, Microbial , HeLa Cells , Humans , Hydrogen-Ion Concentration , Viral Plaque AssayABSTRACT
Arildone (also known as Win 38020), a novel aryl diketone, inhibited replication of herpes simplex virus type 2 in tissue culture by interfering with an event that occurs prior to 6 h postinfection. The inhibition could be partially reversed by washing. Although the exact mechanism of action is unknown, neither viral deoxyribonucleic acid nor viral proteins were synthesized in the presence of arildone.