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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.

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.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Chu CK,Yadav V,Chong YH,Schinazi RF

doi

10.1021/jm050060l

keywords:

subject

Has Abstract

pub_date

2005-06-16 00:00:00

pages

3949-52

issue

12

eissn

0022-2623

issn

1520-4804

journal_volume

48

pub_type

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