ArticleJournal of virology2001
Viral evolution in response to the broad-based retroviral protease inhibitor TL-3.
Article in Journal of virology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 29 citations in OpenAlex.
- The AutoDock suite at 30.Protein science : a publication of the Protein Society · 2021Article
- Selection of drug-resistant feline immunodeficiency virus (FIV) encoding FIV/HIV chimeric protease in the presence of HIV-specific protease inhibitors.Journal of virology · 2013Article
- Small molecule regulation of protein conformation by binding in the Flap of HIV protease.ACS chemical biology · 2013Article
- Article
- Structural basis for drug and substrate specificity exhibited by FIV encoding a chimeric FIV/HIV protease.Acta crystallographica. Section D, Biological crystallography · 2011Article
- A cleavage enzyme-cytometric bead array provides biochemical profiling of resistance mutations in HIV-1 Gag and protease.Biochemistry · 2011Article
- Identification of broad-based HIV-1 protease inhibitors from combinatorial libraries.The Biochemical journal · 2010Article
- Generation of infectious feline immunodeficiency virus (FIV) encoding FIV/human immunodeficiency virus chimeric protease.Journal of virology · 2010Article
- Fragment-based screen against HIV protease.Chemical biology & drug design · 2010Article
- A copper(I)-catalyzed 1,2,3-triazole azide-alkyne click compound is a potent inhibitor of a multidrug-resistant HIV-1 protease variant.Journal of medicinal chemistry · 2008Article
- A look inside HIV resistance through retroviral protease interaction maps.PLoS computational biology · 2007Article
- Crystal structure of an FIV/HIV chimeric protease complexed with the broad-based inhibitor, TL-3.Retrovirology · 2007Article
- Altered gag polyprotein cleavage specificity of feline immunodeficiency virus/human immunodeficiency virus mutant proteases as demonstrated in a cell-based expression system.Journal of virology · 2006Article
- Assessment of FIV-C infection of cats as a function of treatment with the protease inhibitor, TL-3.Retrovirology · 2004Article
- Resolution and prevention of feline immunodeficiency virus-induced neurological deficits by treatment with the protease inhibitor TL-3.Journal of virology · 2004Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
TL-3 is a protease inhibitor developed using the feline immunodeficiency virus protease as a model. It has been shown to efficiently inhibit replication of human, simian, and feline immunodeficiency viruses and therefore has broad-based activity. We now demonstrate that TL-3 efficiently inhibits the replication of 6 of 12 isolates with confirmed resistance mutations to known protease inhibitors. To dissect the spectrum of molecular changes in protease and viral properties associated with resistance to TL-3, a panel of chronological in vitro escape variants was generated. We have virologically and biochemically characterized mutants with one (V82A), three (M46I/F53L/V82A), or six (L24I/M46I/F53L/L63P/V77I/V82A) changes in the protease and structurally modeled the protease mutant containing six changes. Virus containing six changes was found to be 17-fold more resistant to TL-3 in cell culture than was wild-type virus but maintained similar in vitro replication kinetics compared to the wild-type virus. Analyses of enzyme activity of protease variants with one, three, and six changes indicated that these enzymes, compared to wild-type protease, retained 40, 47, and 61% activity, respectively. These results suggest that deficient protease enzymatic activity is sufficient for function, and the observed protease restoration might imply a selective advantage, at least in vitro, for increased protease activity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.