{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:27:53Z","timestamp":1791332873884,"version":"4.3.1"},"reference-count":96,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2001,10,1]],"date-time":"2001-10-01T00:00:00Z","timestamp":1001894400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"},{"start":{"date-parts":[[2001,10,1]],"date-time":"2001-10-01T00:00:00Z","timestamp":1001894400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antivir Chem Chemother"],"published-print":{"date-parts":[[2001,10]]},"abstract":"<jats:p>Although ribavirin was originally synthesized over 30 years ago and has been used to treat viral infections as monotherapy (respiratory syncytial virus and Lassa fever virus) or with interferon-\u03b1 (IFN-\u03b1) as combination therapy (hepatitis C virus), the precise mechanism of its therapeutic activities remains controversial. In this review we focus on two main biological properties of ribavirin: its indirect and direct antiviral activities (with particular emphasis on its efficacy against chronic hepatitis C infection). Each property could individually or collectively account for its clinical efficacy against viral infections. First, with emphasis on the evidence for indirect activities of ribavirin, we will review the clinical observations that suggest that the immunomodulatory properties of ribavirin can in part account for its antiviral activities in vivo. We will then describe the mode of ribavirin's direct antiviral activities. These direct activities can be ascribed to several possible mechanisms, including the recently described activity as an RNA mutagen, a property that may be important in driving a rapidly mutating RNA virus over the threshold to \u2018error catastrophe\u2032.<\/jats:p>","DOI":"10.1177\/095632020101200501","type":"journal-article","created":{"date-parts":[[2015,3,16]],"date-time":"2015-03-16T17:01:37Z","timestamp":1426525297000},"page":"261-272","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":106,"title":["Mechanisms of Action of Ribavirin in Antiviral Therapies"],"prefix":"10.1177","volume":"12","author":[{"given":"Robert C","family":"Tam","sequence":"first","affiliation":[{"name":"Research and Development, ICN Pharmaceuticals, Costa Mesa, Calif., USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnson YN","family":"Lau","sequence":"additional","affiliation":[{"name":"Research and Development, ICN Pharmaceuticals, Costa Mesa, Calif., USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Hong","sequence":"additional","affiliation":[{"name":"Research and Development, ICN Pharmaceuticals, Costa Mesa, Calif., USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2001,10,1]]},"reference":[{"key":"bibr1-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199908193410802"},{"key":"bibr2-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(97)70235-X"},{"key":"bibr3-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510260231"},{"key":"bibr4-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510240102"},{"key":"bibr5-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.33.11.2009"},{"key":"bibr6-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2001.21162"},{"key":"bibr7-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1126\/science.2523562"},{"key":"bibr8-095632020101200501","doi-asserted-by":"crossref","first-page":"215A","DOI":"10.1016\/S0168-8278(97)80029-3","volume":"26","author":"Clarysse C","year":"1997","journal-title":"Hepatology"},{"key":"bibr9-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80044-8"},{"key":"bibr10-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1084\/jem.183.1.109"},{"key":"bibr11-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1136\/gut.44.3.424"},{"key":"bibr12-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(00)70217-4"},{"key":"bibr13-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1038\/82191"},{"key":"bibr14-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.111085598"},{"key":"bibr15-095632020101200501","first-page":"33","volume-title":"Clinical Applications of Ribavirin","author":"Crumpacker CS","year":"1984"},{"key":"bibr16-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198911303212203"},{"key":"bibr17-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199811193392102"},{"key":"bibr18-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200103150-00019"},{"key":"bibr19-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1007\/s001090050062"},{"key":"bibr20-095632020101200501","first-page":"89","volume":"19","author":"Doherty P","year":"1974","journal-title":"Transplantation Reviews"},{"key":"bibr21-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(96)80225-X"},{"key":"bibr22-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1016\/S0198-8859(98)00111-6"},{"key":"bibr23-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1099-0496(199803)25:3<154::AID-PPUL4>3.0.CO;2-M"},{"key":"bibr24-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.11.6.946"},{"key":"bibr25-095632020101200501","first-page":"417","volume":"8","author":"Fan FS","year":"1991","journal-title":"Bone Marrow Transplantation"},{"key":"bibr26-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(00)80312-8"},{"key":"bibr27-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1007\/BF00945022"},{"key":"bibr28-095632020101200501","first-page":"103","volume":"20","author":"Farci P","year":"2000","journal-title":"Seminars in Liver Disease"},{"key":"bibr29-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.33.10.1668"},{"key":"bibr30-095632020101200501","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/S0026-895X(25)09567-7","volume":"38","author":"Fernandez-Larsson R","year":"1990","journal-title":"Molecular Pharmacology"},{"key":"bibr31-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(05)80387-3"},{"key":"bibr32-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(08)80271-5"},{"key":"bibr33-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510270530"},{"key":"bibr34-095632020101200501","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.4049\/jimmunol.158.3.1231","volume":"158","author":"Geissler M","year":"1997","journal-title":"Journal of Immunology"},{"key":"bibr35-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(79)91853-9"},{"key":"bibr36-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.1993.tb00734.x"},{"key":"bibr37-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.19.1.65"},{"key":"bibr38-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198306163082403"},{"key":"bibr39-095632020101200501","doi-asserted-by":"crossref","first-page":"394A","DOI":"10.1053\/jhep.2000.9143","volume":"32","author":"He Q","year":"2000","journal-title":"Hepatology"},{"key":"bibr40-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.11.2716"},{"key":"bibr41-095632020101200501","first-page":"354A","volume":"32","author":"Hong Z","year":"1999","journal-title":"Hepatology"},{"key":"bibr42-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-79-10-2381"},{"key":"bibr43-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-32-2-327"},{"key":"bibr44-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2893.1997.tb00178.x"},{"key":"bibr45-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510280332"},{"key":"bibr46-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.17.8074-8081.2001"},{"key":"bibr47-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(99)80307-9"},{"key":"bibr48-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C100349200"},{"key":"bibr49-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)06102-5"},{"key":"bibr50-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.4.859-866.2000"},{"key":"bibr51-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1159\/000171599"},{"key":"bibr52-095632020101200501","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/S0022-3565(25)22681-7","volume":"240","author":"Marquardt DL","year":"1987","journal-title":"Journal of Pharmacology Experimental Therapeutics"},{"key":"bibr53-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1006\/cyto.1997.0333"},{"key":"bibr54-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198601023140104"},{"key":"bibr55-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199811193392101"},{"key":"bibr56-095632020101200501","first-page":"367A","volume":"32","author":"Morishima C","year":"2000","journal-title":"Hepatology"},{"key":"bibr57-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(96)80606-2"},{"key":"bibr58-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510280129"},{"key":"bibr59-095632020101200501","doi-asserted-by":"crossref","first-page":"3487","DOI":"10.4049\/jimmunol.160.7.3487","volume":"160","author":"Ning Q","year":"1998","journal-title":"Journal of Immunology"},{"key":"bibr60-095632020101200501","doi-asserted-by":"crossref","first-page":"629","DOI":"10.2174\/092986730607220401124820","volume":"6","author":"Pankiewicz KW","year":"1999","journal-title":"Current Medicinal Chemistry"},{"key":"bibr61-095632020101200501","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1128\/iai.29.2.583-589.1980","volume":"29","author":"Peavy DL","year":"1980","journal-title":"Infection and Immunity"},{"key":"bibr62-095632020101200501","doi-asserted-by":"crossref","first-page":"861","DOI":"10.4049\/jimmunol.126.3.861","volume":"126","author":"Peavy DL","year":"1981","journal-title":"Journal of Immunology"},{"key":"bibr63-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510240405"},{"key":"bibr64-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.10.2451"},{"key":"bibr65-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(89)90413-3"},{"key":"bibr66-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.70.10.7092-7102.1996"},{"key":"bibr67-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.1890410203"},{"key":"bibr68-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)06088-1"},{"key":"bibr69-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(97)80409-6"},{"key":"bibr70-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2001.21147"},{"key":"bibr71-095632020101200501","doi-asserted-by":"crossref","first-page":"374A","DOI":"10.1016\/S0168-8278(00)80386-4","volume":"32","author":"Rigopoulou EI","year":"2000","journal-title":"Hepatology"},{"key":"bibr72-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(96)80320-5"},{"key":"bibr73-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2000.9635"},{"key":"bibr74-095632020101200501","doi-asserted-by":"publisher","DOI":"10.3109\/00365548909021689"},{"key":"bibr75-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(76)90128-8"},{"key":"bibr76-095632020101200501","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-115-9-700"},{"key":"bibr77-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1126\/science.177.4050.705"},{"key":"bibr78-095632020101200501","first-page":"23","volume-title":"Ribavirin: A Broad Spectrum Antiviral Agent","author":"Sidwell RW","year":"1980"},{"key":"bibr79-095632020101200501","first-page":"19","volume-title":"Clinical Applications of Ribavirin","author":"Sidwell RW","year":"1984"},{"key":"bibr80-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1542\/peds.95.4.500"},{"key":"bibr81-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1016\/S0162-3109(00)00193-4"},{"key":"bibr82-095632020101200501","first-page":"99","volume-title":"Ribavirin: A Broad Spectrum Antiviral Agent","author":"Smith RA","year":"1980"},{"key":"bibr83-095632020101200501","first-page":"1","volume-title":"Clinical Applications of Ribavirin","author":"Smith RA","year":"1984"},{"key":"bibr84-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.70.4.1174"},{"key":"bibr85-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(99)80093-2"},{"key":"bibr86-095632020101200501","doi-asserted-by":"crossref","first-page":"3709","DOI":"10.4049\/jimmunol.163.7.3709","volume":"163","author":"Tam RC","year":"1999","journal-title":"Journal of Immunology"},{"key":"bibr87-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.5.1276-1283.2000"},{"key":"bibr88-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1016\/0168-8278(91)90814-R"},{"key":"bibr89-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.32.4.492"},{"key":"bibr90-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510250233"},{"key":"bibr91-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.75.7.3042"},{"key":"bibr92-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1016\/0166-3542(85)90013-0"},{"key":"bibr93-095632020101200501","first-page":"408A","volume":"30","author":"Wright T","year":"1999","journal-title":"Hepatology"},{"key":"bibr94-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1086\/516459"},{"key":"bibr95-095632020101200501","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.19.9134-9143.2000"},{"key":"bibr96-095632020101200501","first-page":"374A","volume":"30","author":"Zitron IM","year":"2000","journal-title":"Hepatology"}],"container-title":["Antiviral Chemistry and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/095632020101200501","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/095632020101200501","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:45:36Z","timestamp":1747788336000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/095632020101200501"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,10]]},"references-count":96,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2001,10]]}},"alternative-id":["10.1177\/095632020101200501"],"URL":"https:\/\/doi.org\/10.1177\/095632020101200501","relation":{},"ISSN":["0956-3202","2040-2066"],"issn-type":[{"value":"0956-3202","type":"print"},{"value":"2040-2066","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,10]]}}}