The role of 2′,3′-unsaturation on the antiviral activity of anti-HIV nucleosides against 3TC-resistant mutant (M184V)

Molecular modeling studies show that the 2′,3′-double bond of the sugar moiety of various 2′,3′-unsaturated nucleosides interacts with the aromatic moiety of Tyr115 of HIV-1 reverse transcriptase (RT) by hydrophobic π–π interaction. In 3TC-resistant mutant (M184V) RT, 2′-fluoro-2′,3′-unsaturated nucleosides with a bulky 4′-substituent experience significant steric hindrance with the side chain of Val184.