The thiopurine nucleoside analogue 6-methylmercaptopurine riboside (6MMPr) effectively blocks Zika virus replication

Carvalho, Otávio Valério de; Félix, Daniele Mendes; Mendonça, Leila Rodrigues de; Araújo, Catarina M C S; França, Rafael Freitas de Oliveira; Cordeiro, Marli Tenório; Júnior, Abelardo Silva; Pena, Lindomar

doi:10.1016/j.ijantimicag.2017.08.016

Cited by 36 publications

(34 citation statements)

References 37 publications

(44 reference statements)

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“…In addition, the antiviral effect of NAR was evident even when NAR treatment was postponed for 24 hours after infection, and it was similar to IFN-α 2A. Similarly, treatment of ZIKV-infected Vero cells with 6-methylmercaptopurine riboside (6MMPr) 72 hpi impairs viral RNA production and demonstrated the potential use as antiviral compound 64 . Furthermore, some treatments available for flaviviruses, like IFN-α 2A for hepatitis C present several adverse effects, such as pain and depression 65 .…”

Section: Discussionmentioning

confidence: 99%

The citrus flavonoid naringenin impairs the in vitro infection of human cells by Zika virus

Cataneo

Kuczera

Koishi

et al. 2019

Sci Rep

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The Zika virus (ZIKV) is an arthropod-borne virus that belongs to the Flaviviridae family. The ZIKV infection is usually asymptomatic or is associated with mild clinical manifestations; however, increased numbers of cases of microcephaly and birth defects have been recently reported. To date, neither a vaccine nor an antiviral treatment has become available to control ZIKV replication. Among the natural compounds recognized for their medical properties, flavonoids, which can be found in fruits and vegetables, have been found to possess biological activity against a variety of viruses. Here, we demonstrate that the citrus flavanone naringenin (NAR) prevented ZIKV infection in human A549 cells in a concentration-dependent and ZIKV-lineage independent manner. NAR antiviral activity was also observed when primary human monocyte-derived dendritic cells were infected by ZIKV. NAR displayed its antiviral activity when the cells were treated after infection, suggesting that NAR acts on the viral replication or assembly of viral particles. Moreover, a molecular docking analysis suggests a potential interaction between NAR and the protease domain of the NS2B-NS3 protein of ZIKV which could explain the anti-ZIKV activity of NAR. Finally, the results support the potential of NAR as a suitable candidate molecule for developing anti-ZIKV treatments.

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Section: Discussionmentioning

confidence: 99%

The citrus flavonoid naringenin impairs the in vitro infection of human cells by Zika virus

Cataneo

Kuczera

Koishi

et al. 2019

Sci Rep

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“…Chloroquine, a common antimalarial agent, is a good example of the FDA-approved drugs that could be repurposed for the treatment and prophylaxis of ZIKV infection. Several independent laboratories demonstrated that chloroquine efficiently blocks ZIKV infection in human NPCs (Delvecchio et al, 2016) and limits vertical transmission in vivo (Cao et al, 2017; de Carvalho et al, 2017; Shiryaev et al, 2017). Chloroquine (and its derivative hydroxychloroquine) inhibits autophagy, which is the proposed mechanism of its anti-ZIKV action since deficiency in an essential autophagy gene, Atg16l1, in mice limited ZIKV vertical transmission, placental and fetal damage, and improved placental and fetal outcomes overall (Cao et al, 2017).…”

Section: Possible Treatments and Drug Development Strategiesmentioning

confidence: 99%

Zika Virus: Origins, Pathological Action, and Treatment Strategies

et al. 2019

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The Zika virus (ZIKV) global epidemic prompted the World Health Organization to declare it a 2016 Public Health Emergency of International Concern. The overwhelming experience over the past several years teaches us that ZIKV and the associated neurological complications represent a long-term world-wide challenge to public health. Although the number of ZIKV cases in the Western Hemisphere has dropped since 2016, the need for basic research and anti-ZIKV drug development remains strong. Re-emerging viruses like ZIKV are an ever-present threat in the 21st century where fast transcontinental travel lends itself to viral epidemics. Here, we first present the origin story for ZIKV and review the rapid progress researchers have made toward understanding of the ZIKV pathology and in the design, re-purposing, and testing–particularly in vivo–drug candidates for ZIKV prophylaxis and therapy ZIKV. Quite remarkably, a short, but intensive, drug-repurposing effort has already resulted in several readily available FDA-approved drugs that are capable of effectively combating the virus in infected adult mouse models and, most importantly, in both preventing maternal-fetal transmission and severe microcephaly in newborns in pregnant mouse models.

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“…Atovaquone, a FDA pregnancy category C drug used to prevent parasitic infections, impairs ZIKV virus production in human cells by inhibiting pyrimidine biosynthesis, and limits ZIKV infection in an ex vivo human placental tissue model [110]. Likewise, 6-methylmercaptopurine riboside [111], 2′-C-methylguanidine, 2′-C-methyladenosine, and 7-deaza-2′-C-methyladenosine inhibit ZIKV replication in cell cultures [105,112,113], and the later one reduces viremia and retards disease signs in mice [113]. Finally, NITD008 [114] and BCX4430 [115] protects immunosuppressed mice, although the later one does not reduce viral loads.…”

Section: Antiviralsmentioning

confidence: 99%

Therapeutic Advances Against ZIKV: A Quick Response, a Long Way to Go

Saiz

2019

Pharmaceuticals

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Zika virus (ZIKV) is a mosquito-borne flavivirus that spread throughout the American continent in 2015 causing considerable worldwide social and health alarm due to its association with ocular lesions and microcephaly in newborns, and Guillain–Barré syndrome (GBS) cases in adults. Nowadays, no licensed vaccines or antivirals are available against ZIKV, and thus, in this very short time, the scientific community has conducted enormous efforts to develop vaccines and antivirals. So that, different platforms (purified inactivated and live attenuated viruses, DNA and RNA nucleic acid based candidates, virus-like particles, subunit elements, and recombinant viruses) have been evaluated as vaccine candidates. Overall, these vaccines have shown the induction of vigorous humoral and cellular responses, the decrease of viremia and viral RNA levels in natural target organs, the prevention of vertical and sexual transmission, as well as that of ZIKV-associated malformations, and the protection of experimental animal models. Some of these vaccine candidates have already been assayed in clinical trials. Likewise, the search for antivirals have also been the focus of recent investigations, with dozens of compounds tested in cell culture and a few in animal models. Both direct acting antivirals (DAAs), directed to viral structural proteins and enzymes, and host acting antivirals (HAAs), directed to cellular factors affecting all steps of the viral life cycle (binding, entry, fusion, transcription, translation, replication, maturation, and egress), have been evaluated. It is expected that this huge collaborative effort will produce affordable and effective therapeutic and prophylactic tools to combat ZIKV and other related still unknown or nowadays neglected flaviviruses. Here, a comprehensive overview of the advances made in the development of therapeutic measures against ZIKV and the questions that still have to be faced are summarized.

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The thiopurine nucleoside analogue 6-methylmercaptopurine riboside (6MMPr) effectively blocks Zika virus replication

Cited by 36 publications

References 37 publications

The citrus flavonoid naringenin impairs the in vitro infection of human cells by Zika virus

The citrus flavonoid naringenin impairs the in vitro infection of human cells by Zika virus

Zika Virus: Origins, Pathological Action, and Treatment Strategies

Therapeutic Advances Against ZIKV: A Quick Response, a Long Way to Go

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