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  • Title: Anti-HIV activity of (-)-(2R,4R)-1- (2-hydroxymethyl-1,3-dioxolan-4-yl)-thymine against drug-resistant HIV-1 mutants and studies of its molecular mechanism.
    Author: Chu CK, Yadav V, Chong YH, Schinazi RF.
    Journal: J Med Chem; 2005 Jun 16; 48(12):3949-52. PubMed ID: 15943470.
    Abstract:
    (-)-(2R,4R)-1-(2-Hydroxymethyl-1,3-dioxolan-4-yl)thymine (DOT) is the first thymidine kinase-activated nucleoside that is significantly active against all of the clinically significant NRTI-resistant HIV-1 mutants, including AZT (D67N/K70R/T215Y/K219Q), Tenofovir (K65R), and Lamivudine (M184V). To understand the molecular mechanism of drug resistance and the antiviral activity of DOT against drug-resistant RTs, molecular modeling studies of DOT-TP complexed with the wild-type (WT) and mutated RT were conducted. The key reason for this interesting antiviral activity profile is the presence of a dioxolane ring.
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