A Derivate of the Antibiotic Doxorubicin Is a Selective Inhibitor of Dengue and Yellow Fever Virus Replication
            <i>In Vitro</i>

Kaptein, Suzanne; Burghgraeve, Tine De; Froeyen, Mathy; Pastorino, Boris; Alen, Marijke; Mondotte, Juan A.; Herdewijn, Piet; Jacobs, Michael; Lamballerie, Xavier de; Schols, Dominique; Gamarnik, Andrea V.; Sztaricskai, Ferenc; Neyts, Johan

doi:10.1128/aac.00686-10

Cited by 79 publications

(80 citation statements)

References 63 publications

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“…Recently, several groups reported the development of infectious serotype 2 DENV (strain TSV01) expressing Renilla luciferase (11)(12)(13). Though this luciferase variant has utility in a number of applications, such as drug discovery, it is considered inferior to firefly luciferase with respect to bioluminescence imaging (14).…”

Section: Engue Virus (Denv) Is An Arthropod-borne Pathogen Of Thementioning

confidence: 99%

Dengue reporter viruses reveal viral dynamics in interferon receptor-deficient mice and sensitivity to interferon effectors in vitro

Schoggins

Dorner

Feulner

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

173

175

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Dengue virus (DENV) is a global disease threat for which there are no approved antivirals or vaccines. Establishing state-of-the-art screening systems that rely on fluorescent or luminescent reporters may accelerate the development of anti-DENV therapeutics. However, relatively few reporter DENV platforms exist. Here, we show that DENV can be genetically engineered to express a green fluorescent protein or firefly luciferase. Reporter viruses are infectious in vitro and in vivo and are sensitive to antiviral compounds, neutralizing antibodies, and interferons. Bioluminescence imaging was used to follow the dynamics of DENV infection in mice and revealed that the virus localized predominantly to lymphoid and gut-associated tissues. The high-throughput potential of reporter DENV was demonstrated by screening a library of more than 350 IFN-stimulated genes for antiviral activity. Several antiviral effectors were identified, and they targeted DENV at two distinct life cycle steps. These viruses provide a powerful platform for applications ranging from validation of vaccine candidates to antiviral discovery. Flaviviridae family that causes significant morbidity and mortality worldwide. Each year, over 50 million people are affected by dengue fever, and ∼500,000 are hospitalized with the more severe dengue hemorrhagic fever (1). The virus is endemic to tropical environments in Southeast Asia, the Pacific, and the Americas, and has recently reemerged as far north as southern Florida (2). Currently, no vaccines or antivirals have been approved for prevention or treatment of DENV infection.Four genetically and antigenically distinct DENV serotypes circulate, and each can be isolated from infected human sera and propagated in cell culture. The pathogenesis and immune response to patient-derived virus can be studied in vitro and in vivo by quantifying viral genomes or antigens. These detection methods are also used to study the molecular virology of DENV with reagents such as virus-like particles (VLPs) and subgenomic replicons. In some cases, VLPs and subgenomic replicons have been engineered to take advantage of reporter proteins, such as luciferase, which can be used in high-throughput screening platforms for discovery of inhibitors of viral entry or replication (3). A caveat to these tools is the inability to fully recapitulate the entire viral life cycle. This can be overcome by launching virus production from full-length infectious molecular clones, which have been generated for DENV serotypes 1, 2, and 4 (4-6).Full-length flavivirus infectious clones are often difficult to work with, largely due to instability in various bacterial cell lines and the inability to rescue sufficient quantities of DNA for downstream applications (7). Additionally, mutagenesis of viral sequences may result in disruption of the various long-range interactions required for establishment of a productive replication complex (8-10). Thus, strategies to generate infectious viruses expressing heterologous sequences have to contend with both sub...

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Section: Engue Virus (Denv) Is An Arthropod-borne Pathogen Of Thementioning

confidence: 99%

Dengue reporter viruses reveal viral dynamics in interferon receptor-deficient mice and sensitivity to interferon effectors in vitro

Schoggins

Dorner

Feulner

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

173

175

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“…79 These bicistronic viruses were developed for other flaviviruses to express reporter proteins. 74,[80][81][82] Nevertheless, these bicistronic flaviviruses were considered to be very unstable, since soon after few rounds of viral replication, the heterologous IRES-bearing cassettes suffered extensive deletions. 74,75 …”

Section: Expression Of Larger Fragments By the Yf17d Virusmentioning

confidence: 99%

The yellow fever 17D virus as a platform for new live attenuated vaccines

Bonaldo

Sequeira

Galler³

2014

Human Vaccines & Immunotherapeutics

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“…Of these, anthracycline compounds inhibit the activity of phospholipase B in a dose-dependent manner [21]. Doxorubicin also inhibits the replication of HIV [22], herpes simplex virus [23], dengue virus, and yellow fever virus [24]. Novel antimicrobial agents might be developed using anthracycline as the lead compound.…”

Section: Discussionmentioning

confidence: 99%

In vitro Synergistic Effects of Anthracycline Antitumor Agents and Fluconazole Against Azole-Resistant Candida albicans Clinical Isolates

S¹

2013

J Dev Drugs

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A Derivate of the Antibiotic Doxorubicin Is a Selective Inhibitor of Dengue and Yellow Fever Virus Replication In Vitro

Abstract: Dengue virus (DENV), of which four serotypes (DENV-1, -2, -3, and -4) are known, and yellow fever virus (YFV) belong to the mosquito-borne cluster of the genus Flavivirus (family

Cited by 79 publications

References 63 publications

Dengue reporter viruses reveal viral dynamics in interferon receptor-deficient mice and sensitivity to interferon effectors in vitro

Dengue reporter viruses reveal viral dynamics in interferon receptor-deficient mice and sensitivity to interferon effectors in vitro

The yellow fever 17D virus as a platform for new live attenuated vaccines

In vitro Synergistic Effects of Anthracycline Antitumor Agents and Fluconazole Against Azole-Resistant Candida albicans Clinical Isolates

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