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

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.