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• W3034642004 abstract "The ProTide approach has emerged as a powerful tool to improve the intracellular delivery of nucleotide analogs with antiviral and anticancer activity. Here, we characterized the anti-ZIKV (ZIKV, Zika virus) activity of two ProTides of 2′-C-β-methylguanosine. ProTide UMN-1001 is a 2′-C-β-methylguanosine tryptamine phosphoramidate monoester, and ProTide UMN-1002 is a 2-(methylthio)-ethyl-2′-C-β-methylguanosine tryptamine phosphoramidate diester. UMN-1002 undergoes stepwise intracellular activation to the corresponding nucleotide monophosphate followed by P–N bond cleavage by intracellular histidine triad nucleotide binding protein 1 (Hint1). UMN-1001 is activated by Hint1 but is less cell-permeable than UMN-1002. UMN-1001 and UMN-1002 were found to be more potent than 2′-C-β-methylguanosine against ZIKV in human-derived microvascular endothelial and neuroblastoma cells and in reducing ZIKV RNA replication. Studies with a newborn mouse model of ZIKV infection demonstrated that, while treatment with 2′-C-β-methylguanosine and UMN-1001 was lethal, treatment with UMN-1002 was nontoxic and significantly reduced ZIKV infection. Our data suggests that anchimeric activated ProTides of 2′-C-β-methyl nucleosides should be further investigated for their potential as anti-ZIKV therapeutics." @default.
• W3034642004 created "2020-06-19" @default.
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• W3034642004 date "2020-06-11" @default.
• W3034642004 modified "2023-09-27" @default.
• W3034642004 title "<i>In Vitro</i> and <i>In Vivo</i> Characterization of the Anti-Zika Virus Activity of ProTides of 2′-C-β-Methylguanosine" @default.
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• W3034642004 doi "https://doi.org/10.1021/acsinfecdis.0c00091" @default.
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