2. Academic Validation
  3. Synthesis, antiviral activity, and computational study of β-d-xylofuranosyl nucleoside phosphonates

Synthesis, antiviral activity, and computational study of β-d-xylofuranosyl nucleoside phosphonates

  • Eur J Med Chem. 2023 Jul 5:255:115379. doi: 10.1016/j.ejmech.2023.115379.
Yuqing Xu 1,  Elisabetta Groaz 2,  Jérôme Rihon 1,  Piet Herdewijn 1,  Eveline Lescrinier 3
Affiliations

Affiliations

  • 1 Medicinal Chemistry, Rega Institute for Medical Research, KU Leuven, Herestraat 49, 3000, Leuven, Belgium.
  • 2 Medicinal Chemistry, Rega Institute for Medical Research, KU Leuven, Herestraat 49, 3000, Leuven, Belgium; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35131, Padova, Italy.
  • 3 Medicinal Chemistry, Rega Institute for Medical Research, KU Leuven, Herestraat 49, 3000, Leuven, Belgium. Electronic address: [email protected].
PMID: 37120998 DOI: 10.1016/j.ejmech.2023.115379
Abstract

Molecular dynamics (MD) simulations provided insights into the favorable interactions between xylose nucleosides bearing a phosphonate moiety at their 3'-position and specific residues at the active site of the archetypal RNA-dependent RNA-polymerase (RdRp) of Enterovirus 71. Therefore, a series of xylosyl nucleoside phosphonates with adenine, uracil, cytosine, guanosine, and hypoxanthine as nucleobases were synthesized through multistep sequences starting from a single common precursor. Following Antiviral activity evaluation, the adenine containing analogue was found to possess good Antiviral activity against RNA viruses displaying an EC50 of 12 and 16 μM against measles virus (MeV) and enterovirus-68 (EV-68), respectively, whereas lacking cytotoxicity.

Keywords

Antiviral activity; Molecular dynamics; Nucleoside phosphonates; Xylofuranosyl nucleosides.

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