Comparative activities of several nucleoside analogs against influenza A, B, and C viruses in vitro.
A set of 20 nucleoside analogs were examined for their inhibitory effects on the cytopathogenicity and growth of influenza virus type A, B, and C strains in Madin-Darby canine kidney (MDCK) cells. Among the compounds evaluated, pyrazofurin, 3-deazaguanine, ribavirin, carbodine, and cyclopentenyl cytosine inhibited viral cytopathogenicity at concentrations that were lower than those found cytotoxic for the MDCK cells. No differences were observed in the 50% effective doses (based on inhibition of viral cytopathogenicity) of these five compounds for a number of influenza virus type A (subtypes H1N1 and H3N2), B, and C strains. Pyrazofurin showed the lowest 50% effective dose (0.15 microgram/ml), which was about 20- to 30-fold lower than those of the other four compounds. The selectivity indices of the five compounds, calculated as the ratio of the 50% cytotoxic dose (determined by trypan blue exclusion) to the 50% effective dose, were greater than 100. When the selectivity indices were calculated as the ratios of the 50% inhibitory doses for cellular RNA synthesis to the 50% effective doses, they were greater than 100 for ribavirin, pyrazofurin, and 3-deazaguanine but less than 2 for carbodine and cyclopentenyl cytosine. All five compounds inhibited the growth of influenza virus types A and B in MDCK cells at a concentration which was well below their cytotoxicity threshold for MDCK cells and, therefore, deserve further exploration for their potential in the treatment of influenza virus type A, B, and C infections.
Department of Bacteriology, Fukushima Medical College, Japan.
S
S
Shigeta
K
K
Konno
T
T
Yokota
K
K
Nakamura
E
E
De Clercq
D002478:Cells, Cultured; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D009980:Influenza A virus / Q000187:drug effects* / Q000254:growth & development; D009981:Influenza B virus / Q000187:drug effects* / Q000254:growth & development; D009982:Gammainfluenzavirus / Q000187:drug effects* / Q000254:growth & development; D009705:Nucleosides / Q000494:pharmacology*; D009975:Orthomyxoviridae / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects
D009705:Nucleosides