Polysulfonate suramin inhibits Zika virus infection

Tan, Chee Wah; Sam, I‐Ching; Chong, Wei Lim; Lee, Vannajan Sanghiran; Chan, Yoke Fun

doi:10.1016/j.antiviral.2017.04.017

Cited by 75 publications

(51 citation statements)

References 69 publications

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“…The ELE and MLE showed a more pronounced activity than the other extracts with a protective concentration of the cells higher than 50% at 31.2 µg mL -1 (Figure 3). These concentration values of the leaf extracts are similar to those reported by Tan et al 32 for the anti-parasitic drug suramin, which induced a ZIKV adsorption blockade of 80% at a concentration of 50.0 µg mL -1 . The CBE also showed a significant antiviral activity at the concentration of 125.0 µg mL -1 , displaying lysis plates in smaller amounts when compared to the non-treated viral control.…”

Section: Antiviral Activitysupporting

confidence: 88%

Zika Virus Activity of the Leaf and Branch Extracts of Tontelea micrantha and Its Hexane Extracts Phytochemical Study

Ferreira

Hauck

Duarte

et al. 2018

J. Braz. Chem. Soc.

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The new triterpene friedelan-1,3,21-trione, the known compounds friedelan-3-one, 3β-friedelinol, 3,4-seco-friedelan-3-oic acid, 28-hydroxyfriedelan-3-one, friedelan-3-oxo-28-al, friedelan-3,21-dione, 30-hydroxyfriedelan-3-one, a mixture of 30-hydroxyfriedelan-3-one/21α-hydroxyfriedelan-3-one, 21β-hydroxyfriedelan-3-one, gutta-percha, squalene, and a mixture of palmitic/stearic/oleic acids were isolated from the hexane extracts of leaves and branches of T. micrantha. Their chemical structures were established by Fourier transform infrared spectroscopy (FTIR), gas chromatography (GC), 1D/2D nuclear magnetic resonance (NMR) and comparison with the literature data. All compounds were described for T. micrantha and the genus Tontelea for the first time. The branch and leaf extracts displayed anti-Zika virus activity at the lowest tested concentration of 15.6 µg mL-1 , mainly virucidal effect, and presented no cytotoxicity to Vero cells. Furthermore, the ethyl acetate and methanolic leaf extracts demonstrated the best activities at the concentration of 31.2 and 15.6 µg mL-1 at the viral adsorption and penetration stages, respectively. These results showed that these extracts may be promising candidates for the Zika virus treatment.

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Section: Antiviral Activitysupporting

confidence: 88%

Zika Virus Activity of the Leaf and Branch Extracts of Tontelea micrantha and Its Hexane Extracts Phytochemical Study

Ferreira

Hauck

Duarte

et al. 2018

J. Braz. Chem. Soc.

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“…Multiple flaviviruses, including DENV [18], WNV [19], and JEV [20], are known to use cell surface heparan sulfate as an attachment receptor. However, our previous findings suggested that heparan sulfate has no role in ZIKV infection [21]. Sialic acids are typically found on terminating branches of N-glycans, O-glycans and glycosphingolipids (gangliosides).…”

Section: Introductionmentioning

confidence: 92%

“…Our previous findings suggested that ZIKV does not use cell surface heparan sulfate as an attachment receptor [21]. To test the role of sialic acid in ZIKV infection, we used neuraminidase to remove cell surface sialic acid prior to ZIKV infection.…”

Section: Removal Of Surface Sialic Acid From Vero Cells By Neuraminidmentioning

confidence: 99%

Cell surface α2,3-linked sialic acid facilitates Zika virus internalization

Tan

Hor

Kwek

et al. 2019

Emerging Microbes & Infections

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The emergence of neurotropic Zika virus (ZIKV) raised a public health emergency of global concern. ZIKV can cross the placental barrier and infect foetal brains, resulting in microcephaly, but the pathogenesis of ZIKV is poorly understood. With recent findings reporting AXL as a type I interferon antagonist rather than an entry receptor, the exact entry mechanism remains unresolved. Here we report that cell surface sialic acid plays an important role in ZIKV infection. Removal of cell surface sialic acid by neuraminidase significantly abolished ZIKV infection in Vero cells and human induced-pluripotent stem cells-derived neural progenitor cells. Furthermore, knockout of the sialic acid biosynthesis gene encoding UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase resulted in significantly less ZIKV infection of both African and Asian lineages. Huh7 cells deficient in α2,3-linked sialic acid through knockout of ST3 β-galactoside-α2,3-sialyltransferase 4 had significantly reduced ZIKV infection. Removal of membrane-bound, un-internalized virus with pronase treatment revealed the role of sialic acid in ZIKV internalization but not attachment. Sialyllactose inhibition studies showed that there is no direct interaction between sialic acid and ZIKV, implying that sialic acid could be mediating ZIKV-receptor complex internalization. Identification of α2,3-linked sialic acid as an important host factor for ZIKV internalization provides new insight into ZIKV infection and pathogenesis.

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“…Suramin may also affect ZIKV late in the life cycle, possibly by inhibiting the release of ZIKV progeny. Additionally, in silico studies reveal suramin binds NS3 helicase with greater affinity than ZIKV envelope proteins, which may suggest suramin also inhibits ZIKV replication [64]. Although published findings suggest suramin interacts with multiple ZIKV targets and may inhibit viral entry, replication, and release, no in vivo data have been published to date.…”

Section: Drug Discovery: Viral Targets Attachment Endocytosis and Fmentioning

confidence: 99%

Therapeutic Approaches for Zika Virus Infection of the Nervous System

2017

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Zika virus has spread rapidly in the Americas and has caused devastation of human populations affected in these regions. The virus causes teratogenic effects involving the nervous system, and in adults and children can cause a neuropathy similar to Guillain-Barré syndrome, an anterior myelitis, or, rarely, an encephalitis. While major efforts have been undertaken to control mosquito populations that spread the virus and to develop a vaccine, drug development that directly targets the virus in an infected individual to prevent or treat the neurological manifestations is necessary. Rational and targeted drug development is possible since the viral life cycle and the structure of the key viral proteins are now well understood. While several groups have identified therapeutic candidates, their approaches differ in the types of screening processes and viral assays used. Animal studies are available for only a few compounds. Here we provide an exhaustive review and compare each of the classes of drugs discovered, the methods used for drug discovery, and their potential use in humans for the prevention or treatment of neurological complications of Zika virus infection.

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Polysulfonate suramin inhibits Zika virus infection

Cited by 75 publications

References 69 publications

Zika Virus Activity of the Leaf and Branch Extracts of Tontelea micrantha and Its Hexane Extracts Phytochemical Study

Zika Virus Activity of the Leaf and Branch Extracts of Tontelea micrantha and Its Hexane Extracts Phytochemical Study

Cell surface α2,3-linked sialic acid facilitates Zika virus internalization

Therapeutic Approaches for Zika Virus Infection of the Nervous System

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