Efficacy of Ribavirin Against Influenza Virus in Tissue Culture and in Mice

Durr, Frederick E.; Lindh, H. F.

doi:10.1111/j.1749-6632.1975.tb29244.x

Cited by 15 publications

(13 citation statements)

References 6 publications

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“…felbinac, apigenin, prednisone) and adrenergic agonists/antagonists (timolol, methoxamine, tolazoline), as represented in the Venn diagram ( Figure 1D , Table 1 ). Interestingly, at least 14 (40%) molecules from our short-list belong to a pharmacological class related with anti-microbial or anti-inflammatory activities ( Table 1 , #), and 11 (31.4%) have already been reported in the literature for their antiviral properties against influenza or other viruses ( Table 1 , *), notably the nucleoside inhibitor ribavirin [38, 39] and the ionophore monensin [40].…”

Section: Resultsmentioning

confidence: 99%

Repurposing of drugs as novel influenza inhibitors from clinical gene expression infection signatures

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Terrier

Lamballerie

et al. 2018

Preprint

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42Background: Influenza virus infections remain a major and recurrent public health burden. The 43 intrinsic ever-evolving nature of this virus, the suboptimal efficacy of current influenza 44 inactivated vaccines, as well as the emergence of resistance against a limited antiviral arsenal, 45 highlight the critical need for novel therapeutic approaches. In this context, the aim of this study 46 was to develop and validate an innovative strategy for drug repurposing as host-targeted 47 inhibitors of influenza viruses and the rapid evaluation of the most promising candidates in Phase 48 II clinical trials. 49 Methods:We exploited in vivo global transcriptomic signatures of infection directly obtained 50 from a patient cohort to determine a shortlist of already marketed drugs with newly identified, 51 host-targeted inhibitory properties against influenza virus. The antiviral potential of selected 52 repurposing candidates was further evaluated in vitro, in vivo and ex vivo. 53 Results: Our strategy allowed the selection of a shortlist of 35 high potential candidates out of a 54 rationalized computational screening of 1,309 FDA-approved bioactive molecules, 31 of which 55 were validated for their significant in vitro antiviral activity. Our in vivo and ex vivo results 56 highlight diltiazem, a calcium channel blocker currently used in the treatment of hypertension, as 57 a promising option for the treatment of influenza infections. Additionally, transcriptomic 58 signature analysis further revealed the so far undescribed capacity of diltiazem to modulate the 59 expression of specific genes related to the host antiviral response and cholesterol metabolism.60 Finally, combination treatment with diltiazem and virus-targeted oseltamivir neuraminidase 61 inhibitor further increased antiviral efficacy, prompting rapid authorization for the initiation of a 62 Phase II clinical trial. 63 4Conclusions: This original, host-targeted, drug repurposing strategy constitutes an effective and 64 highly reactive process for the rapid identification of novel anti-infectious drugs, with potential 65 major implications for the management of antimicrobial resistance and the rapid response to 66 future epidemic or pandemic (re)emerging diseases for which we are still disarmed. 67 68 5 Background 69 Besides their well-known pandemic potential, annual outbreaks caused by influenza viruses 70 account for several million respiratory infections and 250,000 to 500,000 deaths worldwide [1]. 71 This global high morbidity and mortality of influenza infections represents a major and recurrent 72 public health threat with high economic burden. In this context, the suboptimal vaccine coverage 73 and efficacy, coupled with recurrent events of viral resistance against a very limited antiviral 74 portfolio, emphasize an urgent need for innovative treatment strategies presenting fewer 75 obstacles for their clinical use [2]. 76 For decades, the strategy for antiviral development was mostly based on serial screenings of 77 hundreds of thousand...

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Section: Resultsmentioning

confidence: 99%

Repurposing of drugs as novel influenza inhibitors from clinical gene expression infection signatures

Pizzorno

Terrier

Lamballerie

et al. 2018

Preprint

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“…An abundance of influenza viral load data exists (e.g., [12, 14, 23, 29, 44, 59, 64, 86, 94, 95, 99, 104, 110]), some of which has been used in modeling studies [2, 6, 38, 39, 46, 47, 65, 68, 82, 85, 89], but analyzing only this type of data may result in exclusion of important dynamics. For example, a recent study comparing influenza infections in aged and adult mice [99] and another comparing influenza strains [62] suggest that lung immunopathology, rather than viral load, is a better indicator of disease severity.…”

Section: Discussionmentioning

confidence: 99%

Influenza A virus infection kinetics: quantitative data and models

Smith

Perelson

2010

WIREs Mechanisms of Disease

153

194

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Influenza A virus is an important respiratory pathogen that poses a considerable threat to public health each year during seasonal epidemics and even more so when a pandemic strain emerges. Understanding the mechanisms involved in controlling an influenza infection within a host is important and could result in new and effective treatment strategies. Kinetic models of influenza viral growth and decay can summarize data and evaluate the biological parameters governing interactions between the virus and the host. Here we discuss recent viral kinetic models for influenza. We show how these models have been used to provide insight into influenza pathogenesis and treatment, and we highlight the challenges of viral kinetic analysis, including accurate model formulation, estimation of important parameters, and the collection of detailed data sets that measure multiple variables simultaneously.

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“…Ribavirin (RBV), the nucleoside analogue 1-␤-D-ribofuranosyl-1,2,4-triazole-3-carboxamide, exhibits antiviral activity against a variety of RNA viruses in cell culture, 9,10 including viruses from the Paramyxoviridae, 11,12 Flaviviridae, [12][13][14] Picornaviridae, 15 Orthomyxoviridae, 16 Arenaviridae, 17,18 and Bunyaviridae 19,20 families. In humans, RBV is used clinically to treat infections by hepatitis C virus (in combination with interferon-␣), 21,22 respiratory syncytial virus, 23 and Lassa fever virus.…”

Section: Introductionmentioning

confidence: 99%

In Vitro and in Vivo Studies of Ribavirin Action on Brazilian Orthobunyavirus

Livonesi¹,

Sousa²,

Badra³

et al. 2006

The American Journal of Tropical Medicine and Hygiene

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Oropouche, Caraparu, Guama, Guaroa, and Tacaiuma are viruses (genus Orthobunyavirus) that cause human febrile illnesses and encephalitis. The goal of this study was to evaluate the antiviral action of ribavirin on these orthobunyaviruses to achieve a therapeutical agent to treat the diseases caused by these viruses. In vitro results showed that ribavirin (50 microg/mL) had antiviral activity only on the Tacaiuma virus. Addition of guanosine in the culture reversed the antiviral effect of ribavirin on Tacaiuma virus, suggesting that ribavirin inhibited this virus by reducing the intra-cellular guanosine pool. Moreover, ribavirin was not an effective drug in vivo because it was unable to inhibit the death of the mice or virus replication in the brain. The results suggest that ribavirin has no antiviral activity on the Oropouche, Caraparu, Guama, Guaroa, or Tacaiuma viruses; consequently, ribavirin would not be a good therapeutical agent to treat these arboviruses.

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Efficacy of Ribavirin Against Influenza Virus in Tissue Culture and in Mice

Cited by 15 publications

References 6 publications

Repurposing of drugs as novel influenza inhibitors from clinical gene expression infection signatures

Repurposing of drugs as novel influenza inhibitors from clinical gene expression infection signatures

Influenza A virus infection kinetics: quantitative data and models

In Vitro and in Vivo Studies of Ribavirin Action on Brazilian Orthobunyavirus

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