PMID: 7517553Jul 5, 1994Paper

Human immunodeficiency virus 1 (HIV-1)-specific reverse transcriptase (RT) inhibitors may suppress the replication of specific drug-resistant (E138K)RT HIV-1 mutants or select for highly resistant (Y181C-->C181I)RT HIV-1 mutants

Proceedings of the National Academy of Sciences of the United States of America
J BalzariniE de Clercq

Abstract

Mutant HIV-1 that expresses a Glu138-->Lys substitution in its RT [(E138K)RT] is resistant to the HIV-1-specific RT inhibitor 2',5'-bis-O-(tert-butyldimethylsilyl)-3'-spiro-5"-(4"-amino-1",2"- oxathiole-2",2"-dioxide)pyrimidine (TSAO). However, cell cultures infected with this mutant were completely protected against virus-mediated destruction by micromolar concentrations of the HIV-1-specific RT inhibitors tetrahydroimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-one and -thione (TIBO), nevirapine, and bis(heteroaryl)piperazine (BHAP). In contrast, cells infected with a virus mutant that expresses a Tyr181-->Cys substitution in its RT [(Y181C)RT] were not protected by nevirapine and TIBO and were only temporarily protected by BHAP. HIV-1 mutant that emerged under the latter conditions contained a Cys181-->Ile substitution in their RT [(LC181I)RT]. This mutant proved highly resistant to all HIV-1-specific RT inhibitors tested, except for several 1-(2-hydroxyethoxymethyl)-6-(phenylthio)thymine (HEPT) derivatives. When recombinant (C181I)RT was evaluated for susceptibility to the HIV-1-specific RT inhibitors, it was resistant to all inhibitors except the HEPT compounds. Since a (Y181F)RT HIV mutant strain was isolated from cells infect...Continue Reading

References

Nov 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·C K ShihJ A Griffin
Dec 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·D RichmanJ Griffin
Aug 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·R J ColonnoM A Murcko
May 1, 1993·Antimicrobial Agents and Chemotherapy·T J DuewekeL Resnick

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Citations

Jan 1, 1996·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·E De Clercq
Oct 6, 2000·AIDS Research and Human Retroviruses·P B GilbertR T D'Aquila
Apr 5, 2002·Clinical Microbiology Reviews·Robert W Shafer
Jul 2, 2005·Expert Opinion on Emerging Drugs·M L AndreolaM Legraverend
Apr 1, 1995·Nature Structural Biology·J RenD Stuart
Jun 4, 2011·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Lotke TambuyzerJohan Vingerhoets
Aug 18, 2020·Computational Biology and Chemistry·Pooja Balasaheb ShindeMd Ataul Islam
Oct 23, 1997·Clinical Microbiology Reviews·E De Clercq

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