Discovery of wild-type and Y181C mutant non-nucleoside HIV-1 reverse transcriptase inhibitors using virtual screening with multiple protein structures.

Abstract:

:To discover non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs) that are effective against both wild-type (WT) virus and variants that encode the clinically troublesome Tyr181Cys (Y181C) RT mutation, virtual screening by docking was carried out using three RT structures and more than 2 million commercially available compounds. Two of the structures are for WT-virus with different conformations of Tyr181, while the third structure incorporates the Y181C modification. Eventually nine compounds were purchased and assayed. Three of the compounds show low-micromolar antiviral activity toward either or both the wild-type and Y181C HIV-1 strains. The study illustrates a viable protocol to seek anti-HIV agents with enhanced resistance profiles.

journal_name

J Chem Inf Model

authors

Nichols SE,Domaoal RA,Thakur VV,Tirado-Rives J,Anderson KS,Jorgensen WL

doi

10.1021/ci900068k

subject

Has Abstract

pub_date

2009-05-01 00:00:00

pages

1272-9

issue

5

eissn

1549-9596

issn

1549-960X

journal_volume

49

pub_type

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