Enantioselectivity of the antiviral effects of nucleoside analogues.

Natural D-nucleosides are no longer the sole basis for designing effective antiviral analogues. Many antivirals with an opposite (L) configuration were reported, with lamivudine being the most notable example. In contrast, carbocyclic nucleoside analogues are significantly more enantioselective, and enantiomers with a configuration corresponding to D-nucleosides are usually favored. In the series of acyclic nucleoside analogues, the antiviral potency resides in a single enantiomer. Allenic analogues with an axial dissymmetry are R-enantioselective, in contrast to structurally similar methylenecyclopropanes, where the enantioselectivity strongly depends on the type of virus. Enantioselectivity of acyclic nucleotide analogues exhibits a more complex pattern. The overall enantioselectivity of the antiviral effects is determined by responses of activating (phosphorylating) enzymes, as well as target DNA polymerases (reverse transcriptase), toward enantiomers of active analogues.