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

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.