Anti-influenza virus activity of the neuraminidase inhibitor 4-guanidino-Neu5Ac2en in cell culture and in human respiratory epithelium.
The anti-influenza activity of the neuraminidase inhibitor 4-guanidino-Neu5Ac2en (4-G-NAc) was determined in Madin-Darby canine kidney (MDCK) cells by yield reduction and ELISA and in explants of human respiratory epithelium by yield reduction. In MDCK cells, 50% inhibitory concentrations (EC50) averaged 0.5 microgram/ml for influenza A/Virginia/88(H3N2) and 0.04 microgram/ml for A/Texas/36/91(H1N1) by ELISA, and < 0.01 microgram/ml for influenza A/Virginia by yield reduction. In human adenoid explants, concentrations causing at least 1.0 log10 TCID50/ml decrease in yield (EC90) at 48 h were < 0.01 microgram/ml for A(H1N1) and A(H3N2) viruses and 0.25 microgram/ml for B/Hong Kong/5/72. 100 micrograms/ml 4-G-NAc did not inhibit outgrowth of human adenoid epithelium at 6 days, whereas ribavirin 10 micrograms/ml reduced outgrowth by > 50%. 4-G-NAc is a potent and selective inhibitor of clinical isolates of influenza A and B viruses in human respiratory epithelium.
Hayden
F G
FG
Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville 22908.
Rollins
B S
BS
Madren
L K
LK
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D004285:Dogs; D004848:Epithelium / Q000821:virology; D006146:Guanidines; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects* / Q000502:physiology; D009981:Influenza B virus / Q000187:drug effects* / Q000502:physiology; D007668:Kidney; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D009924:Organ Culture Techniques; D011714:Pyrans; D012137:Respiratory System / Q000166:cytology / Q000821:virology*; D012254:Ribavirin / Q000494:pharmacology; D012299:Rimantadine / Q000494:pharmacology; D012794:Sialic Acids / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects; D053243:Zanamivir
D000998:Antiviral Agents; D006146:Guanidines; D011714:Pyrans; D012794:Sialic Acids; D012299:Rimantadine; D012254:Ribavirin; D009439:Neuraminidase; D053243:Zanamivir