Evaluation of Sofosbuvir (β-D-2′-deoxy-2′-α-fluoro-2′-β-C-methyluridine) as an inhibitor of Dengue virus replication
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Xu, Hongtao; Colby-Germinario, Susan P.; Hassounah, Said; Fogarty, Clare; Osman, Nathan; Palanisamy, Navaneethan; Han, Ying-Shan; Oliveira, Maureen; Quan, Yudong; Wainberg, Mark A.

doi:10.1038/s41598-017-06612-2

Cited by 63 publications

(66 citation statements)

References 54 publications

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“…Considering that these agents belong to the same family of viruses, it was plausible to test sofosbuvir against YFV.Indeed, we observed that sofosbuvir predictively targets the YFV RNA RNA polymerase in silico and by dose response antiviral assays. In fact, the in vitro antiviral results display that sofosbuvir`s EC50% towards YFV is in micromolar range and comparable to what has been described for ZIKV and DENV (9)(10)(11). Sofosbuvir`s metabolism is complex and some facets are clearly undescribed.…”

Section: -Discussionmentioning

confidence: 67%

“…Several groups demonstrated that the clinically approved anti-HCV drug sofosbuvir is endowed with antiviral activity towards other flavivirus such as ZIKV (9, 10) and DENV (11). Considering that these agents belong to the same family of viruses, it was plausible to test sofosbuvir against YFV.Indeed, we observed that sofosbuvir predictively targets the YFV RNA RNA polymerase in silico and by dose response antiviral assays.…”

Section: -Discussionmentioning

confidence: 78%

“…Our group has recently shown that sofosbuvir, a clinically approved anti-hepatitis C virus (HCV) drug, is also endowed with anti-Zika virus (ZIKV) antiviral activity in vitro and in vivo models (9,10). Others have demonstrated that sofosbuvir also block dengue virus (DENV) replication (11). Sofosbuvir was approved by food and drug administration (FDA) in 2013.…”

Section: -Introductionmentioning

confidence: 99%

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Yellow fever virus is susceptible to sofosbuvir both in vitro and in vivo

Freitas

Higa

Sacramento

et al. 2018

Preprint

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Yellow fever virus (YFV) is a member of the Flaviviridae family, that causes major mortality. In Brazil, YFV activity increased in the last years. It has been registered that sylvatic, instead of urban, yellow fever (YF) leads our contemporary public health concern. Low vaccinal coverage leaves the human population near the jangle vulnerable to the outbreak, making it necessary to identify therapeutic options. Repurposing of clinically approved antiviral drugs represents an alternative for such identification. Other Flaviviruses, such Zika (ZIKV) and dengue (DENV) viruses, are susceptible to Sofosbuvir, a clinically approved drug against hepatitis C virus (HCV). Moreover, sofosbuvir has a safety record on critically ill hepatic patients, making it an attractive option. Our data show that YFV RNA polymerase uses conserved amino acid resides for nucleotide binding to dock sofosbuvir. This drug inhibited YFV replication in different lineages of human hepatoma cells, Huh-7 and HepG2, with EC50 value of 4.8 µM.Sofosbuvir protected YFV-infected neonatal Swiss mice from mortality and weight loss.Our pre-clinical results indicate that sofosbuvir could represent an option against YFV.

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Section: -Discussionmentioning

confidence: 67%

Section: -Discussionmentioning

confidence: 78%

Section: -Introductionmentioning

confidence: 99%

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Yellow fever virus is susceptible to sofosbuvir both in vitro and in vivo

Freitas

Higa

Sacramento

et al. 2018

Preprint

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“…It has been found that HCV and ZIKV RNA polymerases have very similar active sites, confirming that sofosbuvir could also act on ZIKV-infected cells. It was also demonstrated via cellular assays and animal models that sofosbuvir inhibits the replication of other flaviviruses, such as dengue virus (DENV) (Xu et al, 2017), yellow fever virus (YFV) , and chikungunya virus (CHIKV) .…”

Section: Introductionmentioning

confidence: 99%

Selected nucleos(t)ide-based prescribed drugs and their multi-target activity

Pastuch-Gawołek

Gillner

Król

et al. 2019

European Journal of Pharmacology

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A B S T R A C T Nucleos(t)ide analogues play pivotal roles as antiviral, cytotoxic or immunosuppressive agents. Here, we review recent reports of nucleoside analogues that exhibit broad-spectrum activity towards multiple life-threatening RNA and DNA viruses. We also present a discussion about nucleoside antimetabolites-approved antineoplastic agents-that have recently been shown to have antiviral and/or antibacterial activity. The approved drugs and drug combinations, as well as recently identified candidates for investigation and/or experimentation, are discussed. Several examples of repurposed drugs that have already been approved for use are presented. This strategy can be crucial for the first-line treatment of acute infections or coinfections and for the management of drug-resistant strains.T against viral infections of great medical importance (e.g., herpes simplex virus (HSV), varicella zoster virus (VZV), human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV)) and/or that are known antineoplastic agents used to treat cancer. Approved nucleos(t)ide-based drugs with multi-target activity and compounds being tested in clinical trials or evaluated in preclinical assays are listed in Table 1. In this paper, the term "approval date" means the date on which the drug was approved by the US Food and Drug Administration (FDA) unless otherwise stated. G. Pastuch-Gawołek, et al. Multi-target nucleos(t)ide-based drugs in the treatment and prophylaxis of HIV, HBV and HCV infections

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“…We, and others, have demonstrated that sofosbuvir, a clinically approved against hepatitis C virus (HCV) (11-13), also inhibits the replication of flaviviruses, like ZIKV, DENV and yellow fever virus (YFV) (14-19). Sofosbuvir is a safe and a well-tolerated drug, from 400 to 1200 mg daily in 24 weeks regimen.…”

Section: Introductionmentioning

confidence: 99%

Beyond members of the Flaviviridae family, sofosbuvir also inhibits chikungunya virus replication

Ferreira

Reis

Freitas

et al. 2018

Preprint

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Chikungunya virus (CHIKV) causes a febrile disease associated with chronic arthralgia, which 52 may progress to neurological impairment. Chikungunya fever (CF) is a consolidated public health problem, 53 in tropical and subtropical regions of the world, where control of CHIKV vector, mosquitos of the Aedes 54 genus, failed. Since there is no vaccine or specific treatment against CHIKV, infected patients receive only 55 palliative care to alleviate pain and arthralgia. Thus, drug repurposing is necessary to identify antivirals 56 against CHIKV. Recently, the structure and activity of CHIKV RNA polymerase was partially resolved, 57 revealing similar aspects with the enzyme counterparner on other positive sense RNA viruses, such as 58 members of the Flaviviridae family. We then evaluated if sofosbuvir, clinically approved against hepatitis C 59 virus RNA polymerase, which also aims to dengue, Zika and yellow fever viruses replication, would inhibit 60 CHIKV replication. Indeed, sofosbuvir was 5-times more selective in inhibiting CHIKV production in 61 human hepatoma cells than ribavirin, a pan-antiviral drug. Although CHIKV replication in human induced 62 pluripotent stem cell (iPS)-derived astrocytes was less sensitive to sofosbuvir's, compared to hepatoma cells 63 this drug still impaired virus production and cell death in a MOI-dependent manner. Sofosbuvir also 64 exhibited antiviral activity in vivo, by preventing CHIKV-induced paw oedeme in adult mice, at 20 65 mg/kg/day, and mortality on neonate mice model, at 40 and 80 mg/kg/day. Our data demonstrates that a 66 prototypic alphavirus, CHIKV, is also susceptible to sofosbuvir. Since this is a clinically approved drug, it 67 could pave the way to become a therapeutic option against CF. 68 69 70 71 72 73 74 75 76 77 78 4 1. Introduction 79 Chikungunya virus (CHIKV) is a member of the Togaviridae family, genus alphavirus, which 80 causes febrile debilitating illness associated with arthralgia and skin rash (1). Although prolonged and 81 debilitating joint pain and oedema differentiate CHIKV infection among contemporary arboviruses, like 82 dengue (DENV) and Zika (ZIKV) viruses, most often these agents display similar clinical signs and 83 symptoms during the early phase of infection (1). Severe outcomes of CHIKV infection, leading to acute 84 and convalescent neurological impairment, have also been described (2, 3). 85 Chikungunya fever (CF) is a consolidated public health problem with substantial impact in tropical 86 and subtropical regions of the world, where Aedes spp mosquitoes are prevalent and control measures failed 87(1). In last 5 years, the Americas, African and Eurasian regions have been severely impacted by CHIKV (4). 88For instance, in Brazil, since 2014, the Asian and East-Central-South-African (ECSA) genotypes of CHIKV 89 co-circulate (5-7), highlighting a substantial viral activity in a country historically hyperendemic for DENV. 90Since no specific treatment or vaccine against CHIKV exist, repurposing of clinically approved drugs, 91 preferent...

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Evaluation of Sofosbuvir (β-D-2′-deoxy-2′-α-fluoro-2′-β-C-methyluridine) as an inhibitor of Dengue virus replication #

Cited by 63 publications

References 54 publications

Yellow fever virus is susceptible to sofosbuvir both in vitro and in vivo

Yellow fever virus is susceptible to sofosbuvir both in vitro and in vivo

Selected nucleos(t)ide-based prescribed drugs and their multi-target activity

Beyond members of the Flaviviridae family, sofosbuvir also inhibits chikungunya virus replication

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