The broad spectrum antiviral agent ribavirin inhibits capping of mRNA. |
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Authors: | B B Goswami E Borek O K Sharma J Fujitaki R A Smith |
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Institution: | Department of Microbiology, University of Colorado Medical Center, Denver, Colorado 80262 USA;Department of Chemistry, University of California, Los Angeles, California 90024 USA |
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Abstract: | Ribavirin (1-β-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) is a broad spectrum antiviral substance active against a wide range of both DNA and RNA viruses. It is, however, virtually inactive against polio virus. Its pharmacological mechanism of action was obscure. A possible common target for a chemotherapeutic agent in both DNA and RNA viruses is the “capping” reaction of mRNAs which involves the formation of a guanine pyrophosphate structure at the 5′ terminus by mRNA guanylyl transferase. We have observed that Ribavirin triphosphate is a potent competitive inhibitor of the capping guanylation of viral mRNA. This finding could account for the antiviral potency of the drug against both DNA and RNA viruses and its ineffectiveness against a virus in which the mRNAs derived from them are not capped. |
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