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Low-dose ribavirin potentiates the antiviral activity of favipiravir against hemorrhagic fever viruses.

ABSTRACT: Favipiravir is approved in Japan to treat novel or re-emerging influenza viruses, and is active against a broad spectrum of RNA viruses, including Ebola. Ribavirin is the only other licensed drug with activity against multiple RNA viruses. Recent studies show that ribavirin and favipiravir act synergistically to inhibit bunyavirus infections in cultured cells and laboratory mice, likely due to their different mechanisms of action. Convalescent immune globulin is the only approved treatment for Argentine hemorrhagic fever caused by the rodent-borne Junin arenavirus. We previously reported that favipiravir is highly effective in a number of small animal models of Argentine hemorrhagic fever. We now report that addition of low dose of ribavirin synergistically potentiates the activity of favipiravir against Junin virus infection of guinea pigs and another arenavirus, Pichinde virus infection of hamsters. This suggests that the efficacy of favipiravir against hemorrhagic fever viruses can be further enhanced through the addition of low-dose ribavirin.

SUBMITTER: Westover JB

PROVIDER: S-EPMC4724333 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Low-dose ribavirin potentiates the antiviral activity of favipiravir against hemorrhagic fever viruses.

Westover Jonna B JB Sefing Eric J EJ Bailey Kevin W KW Van Wettere Arnaud J AJ Jung Kie-Hoon KH Dagley Ashley A Wandersee Luci L Downs Brittney B Smee Donald F DF Furuta Yousuke Y Bray Mike M Gowen Brian B BB

Antiviral research 20151219

Favipiravir is approved in Japan to treat novel or re-emerging influenza viruses, and is active against a broad spectrum of RNA viruses, including Ebola. Ribavirin is the only other licensed drug with activity against multiple RNA viruses. Recent studies show that ribavirin and favipiravir act synergistically to inhibit bunyavirus infections in cultured cells and laboratory mice, likely due to their different mechanisms of action. Convalescent immune globulin is the only approved treatment for A ...[more]

PMID: 26711718

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Project description:BackgroundCrimean-Congo hemorrhagic fever epidemics often occur in areas where health services are limited, and result in high case fatality rates. Besides intensive care, ribavirin is often recommended. A solid evidence base for the use of this drug will help justify assuring access to the drug in areas where epidemics are common.MethodsWe carried out a systematic review of observational and experimental studies of people with suspected or confirmed Crimean-Congo hemorrhagic fever that included comparisons between patients given ribavirin and those not. We extracted data on mortality, hospital stay, and adverse events. Risk of bias was assessed using a standard checklist, and data were presented in meta-analytical graphs, stratified by study design, and GRADE tables presented. The risk of bias was summarised using the GRADE method.Results21 unique studies, including one randomised controlled trial of ribavirin, were included. Quality of the evidence was very low, with a Down and Black median score of 4 (maximum possible 33). Ribavirin treatment was not shown to be superior to no ribavirin treatment for mortality rate in a single RCT (RR: 1.13, 95%CI: 0.29 to 4.32, 136 participants, GRADE=low quality evidence); but ribavirin was associated with reduced mortality by 44% when compared to no ribavirin treatment in the pooled observational studies (RR: 0.56, 95%CI: 0.35 to 0.90, 955 participants; GRADE=very low quality evidence). Adverse events were more common with the ribavirin patients, but no severe adverse events were reported. No difference in length of hospital stay was reported.ConclusionsNo clear message of benefit is available from the current data on ribavirin as observational data are heavily confounded, and the one trial carried out has limited power. However, ribavirin could potentially have benefits in this condition and these results clearly indicate a pragmatic, randomised controlled trial in the context of good quality supportive care, is urgently needed and ethically justified.

Dataset Information

Low-dose ribavirin potentiates the antiviral activity of favipiravir against hemorrhagic fever viruses.

Publications

Low-dose ribavirin potentiates the antiviral activity of favipiravir against hemorrhagic fever viruses.

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