Antiviral activities of 5-ethynyl-1-beta-D-ribofuranosylimidazole-4- carboxamide and related compounds.
A series of novel compounds, 5-alkynyl-1-beta-D-ribofuranosylimidazole-4- carboxamides, have been identified as broad-spectrum antiviral agents. 5-Ethynyl-1-beta-D-ribofuranosylimidazole-4- carboxamide (EICAR), the most potent congener of the group, showed antiviral potency about 10- to 100-fold greater than that of ribavirin. Similar in spectrum to ribavirin, EICAR was particularly active (50% inhibitory concentration, 0.2 to 4 micrograms/ml) against poxviruses (vaccinia virus), togaviruses (Sindbis and Semliki forest viruses), arenaviruses (Junin and Tacaribe viruses), reoviruses (reovirus type 1), orthomyxoviruses (influenza A and B viruses), and paramyxoviruses (parainfluenza virus type 3, measles virus, subacute sclerosing panencephalitis virus, and respiratory syncytial virus). EICAR was also cytostatic for rapidly growing cells (50% inhibitory concentration, 0.2 to 0.9 microgram/ml). EICAR inhibited vaccinia virus tail lesion formation at doses that were not toxic to the host. EICAR is a candidate antiviral drug for the treatment of pox-, toga-, arena-, reo-, orthomyxo, and paramyxovirus infections.
De Clercq
E
E
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
Cools
M
M
Balzarini
J
J
Snoeck
R
R
Andrei
G
G
Hosoya
M
M
Shigeta
S
S
Ueda
T
T
Minakawa
N
N
Matsuda
A
A
D043383:Adenosylhomocysteinase; D000818:Animals; D000963:Antimetabolites; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004279:DNA, Viral / Q000096:biosynthesis; D006867:Hydrolases / Q000037:antagonists & inhibitors; D051379:Mice; D012367:RNA, Viral / Q000096:biosynthesis; D012254:Ribavirin / Q000494:pharmacology; D012263:Ribonucleosides / Q000494:pharmacology*; D013623:Tail / Q000382:microbiology; D014616:Vaccinia virus / Q000187:drug effects; D014764:Viral Proteins / Q000096:biosynthesis; D014777:Virus Diseases / Q000188:drug therapy / Q000382:microbiology; D014780:Viruses / Q000187:drug effects
D000963:Antimetabolites; D000998:Antiviral Agents; D004279:DNA, Viral; D012367:RNA, Viral; D012263:Ribonucleosides; D014764:Viral Proteins; C059077:5-ethynyl-1-ribofuranosylimidazole-4-carboxamide; D012254:Ribavirin; D006867:Hydrolases; D043383:Adenosylhomocysteinase