Antiviral activity of novel 2′-fluoro-6′-methylene-carbocyclic adenosine against wild-type and drug-resistant hepatitis B virus mutants

Novel 2′-fluoro-6′-methylene-carbocyclic adenosine (9) was synthesized and evaluated its anti-HBV activity. The titled compound demonstrated significant antiviral activity against wild-type as well as lamivudine, adefovir and double lamivudine/entecavir resistant mutants. Molecular modeling study indicate that the 2′-fluoro moiety by a hydrogen bond, as well as the van der Waals interaction of the carbocyclic ring with the phenylalanine moiety of the polymerase promote the positive binding, even in the drug resistant mutants.

Wild-type HBV: EC50 = 1.5 μM. N236T adefovir mutant: EC50 = 1.7 μM. rtLM/rtMV/rtSG entecavir mutant: EC50 = 0.67 μM.Figure optionsDownload as PowerPoint slide