Viruses, Vol. 11, Pages 365: Activity of Selected Nucleoside Analogue ProTides against Zika Virus in Human Neural Stem Cells

Viruses, Vol. 11, Pages 365: Activity of Selected Nucleoside Analogue ProTides against Zika Virus in Human Neural Stem Cells Viruses doi: 10.3390/v11040365 Authors: Jean A. Bernatchez Michael Coste Sungjun Beck Grace A. Wells Lucas A. Luna Alex E. Clark Zhe Zhu David Hecht Jeremy N. Rich Christal D. Sohl Byron W. Purse Jair L. Siqueira-Neto Zika virus (ZIKV), an emerging flavivirus that causes neurodevelopmental impairment to fetuses and has been linked to Guillain-Barré syndrome continues to threaten global health due to the absence of targeted prophylaxis or treatment. Nucleoside analogues are good examples of efficient anti-viral inhibitors, and prodrug strategies using phosphate masking groups (ProTides) have been employed to improve the bioavailability of ribonucleoside analogues. Here, we synthesized and tested a small library of 13 ProTides against ZIKV in human neural stem cells. Strong activity was observed for 2′-C-methyluridine and 2′-C-ethynyluridine ProTides with an aryloxyl phosphoramidate masking group. Substitution of a 2-(methylthio) ethyl phosphoramidate for the aryloxyl phosphoramidate ProTide group of 2′-C-methyluridine completely abolished antiviral activity of the compound. The aryloxyl phosphoramidate ProTide of 2′-C-methyluridine outperformed the hepatitis C virus (HCV) drug sofosbuvir in suppression of viral titers and protection from cytopathic effect...
Source: Viruses - Category: Virology Authors: Tags: Article Source Type: research