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 Modeljournal_title
Journal of chemical information and modelingauthors
Nichols SE,Domaoal RA,Thakur VV,Tirado-Rives J,Anderson KS,Jorgensen WLdoi
10.1021/ci900068ksubject
Has Abstractpub_date
2009-05-01 00:00:00pages
1272-9issue
5eissn
1549-9596issn
1549-960Xjournal_volume
49pub_type
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