Suramin inhibits chikungunya virus replication through multiple mechanisms

Albulescu, Irina C.; Hoolwerff, Marcella van; Wolters, Laura A.; Bottaro, Elisabetta; Nastruzzi, Claudio; Yang, Shih Chi; Tsay, Shwu‐Chen; Hwu, Jih Ru; Snijder, Eric J.; Hemert, Martijn J. van

doi:10.1016/j.antiviral.2015.06.013

Cited by 88 publications

(93 citation statements)

References 37 publications

(57 reference statements)

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“…Suramin is able to inhibit CHIKV infections. This has been observed before by others [26, 27]. However the mode of action is still unclear.…”

Section: Discussionsupporting

confidence: 70%

“…It has a negative charge and binds to basic side chains of proteins. Several viruses have been described to be inhibited by suramin among them HIV [18, 19] HSV-1 [20], HBV [21], HCV [22], dengue virus [23], EV71 [24], Rift Valley Fever Virus [25] and recently also CHIKV [26, 27]. Here, we extended these observations for CHIKV and EBOV by using pseudotyped-lentiviral vectors carrying envelope glycoproteins and using the wild-type viruses.…”

Section: Introductionmentioning

confidence: 99%

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Suramin is a potent inhibitor of Chikungunya and Ebola virus cell entry

Henß

Beck

Weidner

et al. 2016

Virol J

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BackgroundChikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes high fever, rash, and recurrent arthritis in humans. It has efficiently adapted to Aedes albopictus, which also inhabits temperate regions and currently causes large outbreaks in the Caribbean and Latin America. Ebola virus (EBOV) is a member of the filovirus family. It causes the Ebola virus disease (EDV), formerly known as Ebola hemorrhagic fever in humans and has a mortality rate of up to 70 %. The last outbreak in Western Africa was the largest in history and has caused approximately 25,000 cases and 10,000 deaths. For both viral infections no specific treatment or licensed vaccine is currently available. The bis-hexasulfonated naphthylurea, suramin, is used as a treatment for trypanosome-caused African river blindness. As a competitive inhibitor of heparin, suramin has been described to have anti-viral activity.MethodsWe tested the activity of suramin during CHIKV or Ebola virus infection, using CHIKV and Ebola envelope glycoprotein pseudotyped lentiviral vectors and wild-type CHIKV and Ebola virus.ResultsSuramin efficiently inhibited CHIKV and Ebola envelope-mediated gene transfer while vesicular stomatitis virus G protein pseudotyped vectors were only marginally affected. In addition, suramin was able to inhibit wild-type CHIKV and Ebola virus replication in vitro. Inhibition occurred at early time points during CHIKV infection.ConclusionSuramin, also known as Germanin or Bayer-205, is a market-authorized drug, however shows significant side effects, which probably prevents its use as a CHIKV drug, but due to the high lethality of Ebola virus infections, suramin might be valuable against Ebola infections.

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“…Suramin is able to inhibit CHIKV infections. This has been observed before by others [26, 27]. However the mode of action is still unclear.…”

Section: Discussionsupporting

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Suramin is a potent inhibitor of Chikungunya and Ebola virus cell entry

Henß

Beck

Weidner

et al. 2016

Virol J

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“…1D), so we considered whether viral RNA or viral protein was responsible for the up-regulation of miR-223. It was reported that suramin could selectively inhibit the RNA-dependent RNA polymerase of virus, viral RNA synthesis, and viral protein synthesis (30,31). So we treated the infected macrophages with suramin, and we found the viral RNA and viral protein were significantly down-regulated; however, miR-223 up-regulation was still induced along with type I IFN production ( Fig.…”

Section: Vsv-triggered Type I Ifn Induces the Increase In Mir-223 Expmentioning

confidence: 82%

MicroRNA-223 Promotes Type I Interferon Production in Antiviral Innate Immunity by Targeting Forkhead Box Protein O3 (FOXO3)

Chen¹,

Song²,

et al. 2016

Journal of Biological Chemistry

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Effective recognition of viral infection and subsequent triggering of antiviral innate immune responses are essential for the host antiviral defense, which is tightly regulated by multiple regulators, including microRNAs. Previous reports have shown that some microRNAs are induced during virus infection and participate in the regulation of the innate antiviral response. However, whether the type I IFN response is regulated by miR-223 is still unknown. Here, we reported that vesicular stomatitis virus (VSV) infection induced significant up-regulation of miR-223 in murine macrophages. We observed that miR-223 overexpression up-regulated type I IFN expression levels in VSV-infected macrophages. We also demonstrated that miR-223 directly targets FOXO3 to regulate the type I IFN production. Furthermore, type I IFN, which is triggered by VSV infection, is responsible for the up-regulation of miR-223, thus forming a positive regulatory loop for type I IFN production. Our results uncovered a novel mechanism of miR-223-mediated regulation of type I IFN production in the antiviral innate immunity for the first time.Host innate immune response is the first line of defense following viral infection, which recognizes viral components and produces proinflammatory cytokines and interferons (1-8). The IFN family of antiviral cytokines, especially type I IFN, plays pivotal roles in the host antiviral innate immune response. They are known to inhibit viral replication and mediate protection against viral infection (1-4). Type I IFN production during virus infection should be tightly controlled by multiple intracellular regulators to initiate an appropriate immune response for eliminating the invading pathogens and preventing the development of immunopathological conditions; principal among these is the family of interferon regulatory factors (9 -12). Among the interferon regulatory factors, IRF3 and IRF7 are crucial in the host response to virus infection, inducing the transcription of the type I IFN genes, including the Ifn-␤ gene as well as a number of Ifn-␣ genes (13-16). It has been reported that IRF7 is regulated at three different levels, including the transcriptional, post-transcriptional, and post-translational levels. Transcription of the Irf7 gene is induced by viral infection or type I IFN stimulation (17), although the stability of IRF7 is regulated by FOXO3 (18).MicroRNAs (miRNAs) 4 are small, non-coding, regulatory RNAs that range from 18 to 22 nucleotides in length. They are mainly encoded by gene introns but are also sometimes encoded by dedicated genes. The miRNAs regulate the expression of specific target proteins by either inhibiting translation or degrading the corresponding mRNA (19,20). They regulate between one-and two-thirds of the human genome and participate in most of the cell's main functions (including growth, proliferation, differentiation, signal transduction, apoptosis, metabolism, and aging) (21). It has been reported that, with respect to virus infection, miRNAs constitute a critical additional c...

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“…To date, several studies have identified small-molecule inhibitors that inhibit CHIKV replication in cell culture (9)(10)(11)(12)(13)(14). Some nucleoside analogs, such as ribavirin, have also been shown to interfere with CHIKV replication.…”

mentioning

confidence: 99%

Characterization of β- d - N ⁴ -Hydroxycytidine as a Novel Inhibitor of Chikungunya Virus

Ehteshami

Tao

Zandi

et al. 2017

Antimicrob Agents Chemother

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Chikungunya virus (CHIKV) represents a reemerging global threat to human health. Recent outbreaks across Asia, Europe, Africa, and the Caribbean have prompted renewed scientific interest in this mosquito-borne alphavirus. There are currently no vaccines against CHIKV, and treatment has been limited to nonspecific antiviral agents, with suboptimal outcomes. Herein, we have identified ␤-D-N 4 -hydroxycytidine (NHC) as a novel inhibitor of CHIKV. NHC behaves as a pyrimidine ribonucleoside and selectively inhibits CHIKV replication in cell culture.

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Suramin inhibits chikungunya virus replication through multiple mechanisms

Cited by 88 publications

References 37 publications

Suramin is a potent inhibitor of Chikungunya and Ebola virus cell entry

Suramin is a potent inhibitor of Chikungunya and Ebola virus cell entry

MicroRNA-223 Promotes Type I Interferon Production in Antiviral Innate Immunity by Targeting Forkhead Box Protein O3 (FOXO3)

Characterization of β- d - N ⁴ -Hydroxycytidine as a Novel Inhibitor of Chikungunya Virus

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Suramin inhibits chikungunya virus replication through multiple mechanisms

Cited by 88 publications

References 37 publications

Suramin is a potent inhibitor of Chikungunya and Ebola virus cell entry

Suramin is a potent inhibitor of Chikungunya and Ebola virus cell entry

MicroRNA-223 Promotes Type I Interferon Production in Antiviral Innate Immunity by Targeting Forkhead Box Protein O3 (FOXO3)

Characterization of β- d - N 4 -Hydroxycytidine as a Novel Inhibitor of Chikungunya Virus

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Characterization of β- d - N ⁴ -Hydroxycytidine as a Novel Inhibitor of Chikungunya Virus