hiv protease

Summary

Summary: Enzyme of the human immunodeficiency virus that is required for post-translational cleavage of gag and gag-pol precursor polyproteins into functional products needed for viral assembly. HIV protease is an aspartic protease encoded by the amino terminus of the pol gene. EC 3.4.23.-

Top Publications

  1. pmc Drug resistance mutations for surveillance of transmitted HIV-1 drug-resistance: 2009 update
    Diane E Bennett
    World Health Organization, Geneva, Switzerland
    PLoS ONE 4:e4724. 2009
  2. pmc Human immunodeficiency virus reverse transcriptase and protease sequence database
    Soo Yon Rhee
    Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA 94305, USA
    Nucleic Acids Res 31:298-303. 2003
  3. pmc HIV-1 protease and reverse transcriptase mutations for drug resistance surveillance
    Robert W Shafer
    Division of Infectious Diseases, Stanford University, Stanford, California, USA
    AIDS 21:215-23. 2007
  4. pmc Rationale and uses of a public HIV drug-resistance database
    Robert W Shafer
    Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA 94305, USA
    J Infect Dis 194:S51-8. 2006
  5. pmc Virtual screening for HIV protease inhibitors: a comparison of AutoDock 4 and Vina
    Max W Chang
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA
    PLoS ONE 5:e11955. 2010
  6. pmc Detecting and understanding combinatorial mutation patterns responsible for HIV drug resistance
    Jing Zhang
    Department of Statistics, Harvard University, Science Center, 1 Oxford ST, Cambridge, MA 02138, USA
    Proc Natl Acad Sci U S A 107:1321-6. 2010
  7. ncbi Proteochemometric modeling of drug resistance over the mutational space for multiple HIV protease variants and multiple protease inhibitors
    Maris Lapins
    Department of Pharmaceutical Pharmacology, Uppsala University, SE 751 24 Uppsala, Sweden
    J Chem Inf Model 49:1202-10. 2009
  8. ncbi Antiviral drugs in current clinical use
    Erik De Clercq
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B 3000 Leuven, Belgium
    J Clin Virol 30:115-33. 2004
  9. ncbi A catalogue of putative HIV-1 protease host cell substrates
    Francis Impens
    Department of Medical Protein Research and Biochemistry, VIB, B 9000 Ghent, Belgium
    Biol Chem 393:915-31. 2012
  10. pmc Therapeutic potential of HIV protease-activable CASP3
    Kosuke Miyauchi
    AIDS Research Center, National Institute of Infectious Diseases, 1 23 1 Toyama, Shinjuku ku, Tokyo 162 8640, Japan
    Sci Rep 2:359. 2012

Research Grants

  1. DESIGN AND SYNTHESIS OF NONPEPTIDE PROTEASE INHIBITORS
    Arun K Ghosh; Fiscal Year: 2010
  2. DEVELOPMENT OF LIGAND ASSISTED ASYMMETRIC SYNTHESES
    Arun Ghosh; Fiscal Year: 2001
  3. Drug Resistance in Non-Subtype B HIV-1
    Susan Eshleman; Fiscal Year: 2005
  4. Public HIV Drug Resistance Database
    ROBERT WILLIAM SHAFER; Fiscal Year: 2010
  5. Identification of Mulit-Drug Resistant HIV-1 Isolates
    Robert Shafer; Fiscal Year: 2008
  6. Fitness of Enfuvirtide-(T-20)-Resistant HIV-1
    Daniel Kuritzkes; Fiscal Year: 2006
  7. Design and Synthesis of HIV-1 Protease Inhibitors
    AMOS SMITH; Fiscal Year: 2004
  8. SYNTHESIS OF CHLOROPEPTINS, GP120 CD4 BINDING INHIBITORS
    AMOS SMITH; Fiscal Year: 2001
  9. SYNTHESIS OF SPONGISTATIN ANTITUMOR AGENTS
    AMOS SMITH; Fiscal Year: 2007
  10. NMR systems : 2 Bruker Avance 500 Consoles
    AMOS SMITH; Fiscal Year: 2006

Detail Information

Publications271 found, 100 shown here

  1. pmc Drug resistance mutations for surveillance of transmitted HIV-1 drug-resistance: 2009 update
    Diane E Bennett
    World Health Organization, Geneva, Switzerland
    PLoS ONE 4:e4724. 2009
    ..The updated SDRM list has 93 mutations including 34 NRTI-resistance mutations at 15 RT positions, 19 NNRTI-resistance mutations at 10 RT positions, and 40 PI-resistance mutations at 18 protease positions...
  2. pmc Human immunodeficiency virus reverse transcriptase and protease sequence database
    Soo Yon Rhee
    Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA 94305, USA
    Nucleic Acids Res 31:298-303. 2003
    ..Sequence data on two new molecular targets of HIV drug therapy--gp41 (cell fusion) and integrase--will be added to the database in 2003...
  3. pmc HIV-1 protease and reverse transcriptase mutations for drug resistance surveillance
    Robert W Shafer
    Division of Infectious Diseases, Stanford University, Stanford, California, USA
    AIDS 21:215-23. 2007
    ..However, such programs will not produce comparable estimates unless a standardized list of drug-resistance mutations is used to define transmitted resistance...
  4. pmc Rationale and uses of a public HIV drug-resistance database
    Robert W Shafer
    Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA 94305, USA
    J Infect Dis 194:S51-8. 2006
    ..Such genotype-treatment, genotype-phenotype, and genotype-outcome correlations are contained in the Stanford HIV RT and Protease Sequence Database and have specific usefulness...
  5. pmc Virtual screening for HIV protease inhibitors: a comparison of AutoDock 4 and Vina
    Max W Chang
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA
    PLoS ONE 5:e11955. 2010
    ..This study compares AutoDock 4 and AutoDock Vina in the context of virtual screening by using these programs to select compounds active against HIV protease.
  6. pmc Detecting and understanding combinatorial mutation patterns responsible for HIV drug resistance
    Jing Zhang
    Department of Statistics, Harvard University, Science Center, 1 Oxford ST, Cambridge, MA 02138, USA
    Proc Natl Acad Sci U S A 107:1321-6. 2010
    ....
  7. ncbi Proteochemometric modeling of drug resistance over the mutational space for multiple HIV protease variants and multiple protease inhibitors
    Maris Lapins
    Department of Pharmaceutical Pharmacology, Uppsala University, SE 751 24 Uppsala, Sweden
    J Chem Inf Model 49:1202-10. 2009
    ..The model was further used to identify molecular properties of chemical compounds that are important for their inhibition of multimutated protease variants. Our results give directions how to design novel improved inhibitors...
  8. ncbi Antiviral drugs in current clinical use
    Erik De Clercq
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B 3000 Leuven, Belgium
    J Clin Virol 30:115-33. 2004
    ....
  9. ncbi A catalogue of putative HIV-1 protease host cell substrates
    Francis Impens
    Department of Medical Protein Research and Biochemistry, VIB, B 9000 Ghent, Belgium
    Biol Chem 393:915-31. 2012
    ..Our results are further discussed in the context of HIV-1 infection and the complex substrate recognition by the viral protease...
  10. pmc Therapeutic potential of HIV protease-activable CASP3
    Kosuke Miyauchi
    AIDS Research Center, National Institute of Infectious Diseases, 1 23 1 Toyama, Shinjuku ku, Tokyo 162 8640, Japan
    Sci Rep 2:359. 2012
    ..These data suggest that CASP3* has therapeutic potential against both lymphoid malignancies and HIV-1 infection...
  11. pmc HIV-1 protease mutations and protease inhibitor cross-resistance
    Soo Yon Rhee
    Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, California 94305, USA
    Antimicrob Agents Chemother 54:4253-61. 2010
    ....
  12. pmc Induction of T-cell immunity to antiretroviral drug-resistant human immunodeficiency virus type 1
    Ivan Stratov
    Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia
    J Virol 79:7728-37. 2005
    ..This study suggests feasible strategies to further evaluate the potential of limiting antiretroviral drug resistance through induction of T-cell immunity...
  13. pmc Fragment-based screen against HIV protease
    Alexander L Perryman
    Department of Molecular Biology, The Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA
    Chem Biol Drug Des 75:257-68. 2010
    We have employed a fragment-based screen against wild-type (NL4-3) HIV protease (PR) using the Active Sight fragment library and X-ray crystallography. The experiments reveal two new binding sites for small molecules...
  14. pmc HIV-1 protease cleaves eukaryotic initiation factor 4G and inhibits cap-dependent translation
    I Ventoso
    Centro de Biologia Molecular Severo Ochoa, Universidad Autonoma de Madrid, Facultad de Ciencias, Cantoblanco, 28049 Madrid, Spain
    Proc Natl Acad Sci U S A 98:12966-71. 2001
    ..These findings indicate that HIV-1, a member of retrovirus group, shares with picornaviruses the capacity to proteolyze eIF4G...
  15. ncbi Directed evolution of a protein container
    Bigna Wörsdörfer
    Laboratory of Organic Chemistry, Eidgenossische Technische Hochschule ETH Zurich, 8093 Zurich, Switzerland
    Science 331:589-92. 2011
    ..By using a simple electrostatically based tagging system for protein encapsulation, we successfully sequestered HIV protease, a toxic enzyme when produced cytoplasmically, within an engineered lumazine synthase capsid...
  16. ncbi HIV-1 protease: mechanism and drug discovery
    Ashraf Brik
    Department of Chemistry, Skaggs Institute for Chemical Biology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Org Biomol Chem 1:5-14. 2003
  17. pmc Positive selection detection in 40,000 human immunodeficiency virus (HIV) type 1 sequences automatically identifies drug resistance and positive fitness mutations in HIV protease and reverse transcriptase
    Lamei Chen
    Molecular Biology Institute, Center for Genomics and Proteomics, Dept of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California 90095 1570, USA
    J Virol 78:3722-32. 2004
    ..from 1999 to mid-2002. This data set provides a nearly complete mutagenesis of HIV protease and enables the calculation of statistically significant K(a)/K(s) values for each individual amino acid ..
  18. pmc Multiple-basin energy landscapes for large-amplitude conformational motions of proteins: Structure-based molecular dynamics simulations
    Kei Ichi Okazaki
    Graduate School of Natural Science and Technology, Kobe University, Kobe 657 8501, Japan
    Proc Natl Acad Sci U S A 103:11844-9. 2006
    ..The conformational transition rate varies linearly with driving force over a fairly large range. This linearity appears to be a consequence of partial unfolding during the conformational transition...
  19. pmc Natural polymorphisms in the human immunodeficiency virus type 2 protease can accelerate time to development of resistance to protease inhibitors
    Michel Ntemgwa
    McGill University AIDS Centre, Jewish General Hospital, 3755 Cote Ste Catherine Rd, Montreal, Quebec H3T 1E2, Canada
    Antimicrob Agents Chemother 51:604-10. 2007
    ..Thus, natural polymorphisms in HIV-2 may facilitate the selection of PI resistance. The increasing incidence of such polymorphisms in drug-naive HIV-1- and HIV-2-infected persons is of concern...
  20. ncbi The calculated genetic barrier for antiretroviral drug resistance substitutions is largely similar for different HIV-1 subtypes
    David A van de Vijver
    Eijkman Winkler Institute, Department of Virology, University Medical Center Utrecht, G04 614, 3584 CX Utrecht, The Netherlands
    J Acquir Immune Defic Syndr 41:352-60. 2006
    ..This study compared the genetic barrier between subtypes using some 2000 HIV-1 sequences (>600 of non-B subtype) isolated from anti-retroviral-naive patients in Europe...
  21. ncbi Selection and characterization of HIV-1 showing reduced susceptibility to the non-peptidic protease inhibitor tipranavir
    Louise Doyon
    Biological Sciences Department, Boehringer Ingelheim Ltd Research and Development, 2100 Cunard Street, Laval, Que, Canada H7S 2G5
    Antiviral Res 68:27-35. 2005
    ..These results demonstrate that the tipranavir resistance phenotype is associated with complex genotypic changes in the protease. Resistance necessitates the sequential accumulation of multiple mutations...
  22. ncbi Effects of human immunodeficiency virus type 1 transframe protein p6* mutations on viral protease-mediated Gag processing
    Hsu Chen Chiu
    Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan
    J Gen Virol 87:2041-6. 2006
    ..However, the released virions are not processed appropriately and show a greatly reduced viral infectivity. This suggests that the p6* is indispensable during the process of PR-mediated virus particle maturation...
  23. ncbi Increasing HIV type 1 polymorphic diversity but no resistance to antiretroviral drugs in untreated patients from Central African Republic: a 2005 study
    Valerie Marechal
    Institut Pasteur, Bangui, Central African Republic
    AIDS Res Hum Retroviruses 22:1036-44. 2006
    ..The prevalence of drug resistance mutations in this population was therefore clearly under the WHO 5% threshold...
  24. pmc Prevalence, mutation patterns, and effects on protease inhibitor susceptibility of the L76V mutation in HIV-1 protease
    Thomas P Young
    Abbott Molecular, 1300 East Touhy Avenue, Des Plaines, IL 60018 3315, USA
    Antimicrob Agents Chemother 54:4903-6. 2010
    ..L76V was associated with a 2- to 6-fold decrease in susceptibility to lopinavir, darunavir, amprenavir, and indinavir and a 7- to 8-fold increase in susceptibility to atazanavir and saquinavir...
  25. ncbi Anti-HIV-1 protease activity of compounds from Boesenbergia pandurata
    Sarot Cheenpracha
    Department of Chemistry, Faculty of Sciences, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand
    Bioorg Med Chem 14:1710-4. 2006
    ..As regards active constituents contained in B. pandurata rhizomes, hydroxypanduratin A (3) and panduratin A (2) are active principles against HIV-1 PR...
  26. ncbi Assessment of drug resistance mutations in plasma and peripheral blood mononuclear cells at different plasma viral loads in patients receiving HAART
    Choo Beng Chew
    Center for Infectious Diseases and Microbiology Laboratory Systems, ICPMR, Westmead Hospital, Westmead, NSW 2145, Australia
    J Clin Virol 33:206-16. 2005
    ..PBMCs harbor archival proviral DNA, are a major source of HIV and also underdo latent infection during suppressive HAART...
  27. ncbi HIV-1 protease: structure, dynamics, and inhibition
    John M Louis
    Laboratory of Chemical Physics, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Adv Pharmacol 55:261-98. 2007
  28. pmc Evaluating the substrate-envelope hypothesis: structural analysis of novel HIV-1 protease inhibitors designed to be robust against drug resistance
    Madhavi N L Nalam
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA
    J Virol 84:5368-78. 2010
    ....
  29. ncbi Identification of the minimal conserved structure of HIV-1 protease in the presence and absence of drug pressure
    Francesca Ceccherini-Silberstein
    Department of Experimental Medicine, University of Rome Tor Vergata, Italy
    AIDS 18:F11-9. 2004
    ..To define the extent of amino acid protease (PR) conservation in vivo in the absence and presence of pharmacological pressure in a large patient cohort...
  30. ncbi Threshold survey evaluating transmitted HIV drug resistance among public antenatal clinic clients in Addis Ababa, Ethiopia
    Woldaregay Erku Abegaz
    Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Ethiopia
    Antivir Ther 13:89-94. 2008
    ..The World Health Organization (WHO) recently introduced guidelines to address this issue...
  31. ncbi Identification of I50L as the signature atazanavir (ATV)-resistance mutation in treatment-naive HIV-1-infected patients receiving ATV-containing regimens
    Richard Colonno
    Bristol Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut, USA
    J Infect Dis 189:1802-10. 2004
    ..The unique I50L substitution is the signature mutation for resistance to ATV...
  32. pmc Novel method for probing the specificity binding profile of ligands: applications to HIV protease
    Woody Sherman
    Schrodinger, Inc, 120 West 45th Street, New York, NY 10036, USA
    Chem Biol Drug Des 71:387-407. 2008
    ..The results from this conformational ensemble were similar to those from the drug-resistant ensemble, suggesting the use of a conformational wild-type ensemble as a tool to develop escape-mutant-resistant inhibitors...
  33. pmc Diversification and specialization of HIV protease function during in vitro evolution
    Taryn L O'Loughlin
    Department of Biochemistry, Center for Fundamental and Applied Molecular Evolution, Emory University School of Medicine, Rollins Research Center, Atlanta, GA, USA
    Mol Biol Evol 23:764-72. 2006
    ..The gene encoding model enzyme HIV protease was randomly mutated, and the resulting library was expressed in Escherichia coli cells to eliminate cytotoxic ..
  34. ncbi The role of polymorphisms at position 89 in the HIV-1 protease gene in the development of drug resistance to HIV-1 protease inhibitors
    Jorge L Martinez-Cajas
    Division of Infectious Diseases, Department of Medicine, Queens University, Kingston, Ontario, Canada
    J Antimicrob Chemother 67:988-94. 2012
    ..In subtype B viruses, L89 is commonly found at position 89 in the HIV protease (PR) gene, whereas M89 is commonly observed as a polymorphism in other subtypes...
  35. ncbi Molecular characterization of HIV type 1 in Brazzaville, Republic of Congo, and first data on resistance to antiretroviral drugs
    Mathilde Pircher
    Laboratoire de Virologie WHO accredited, CHU de Bordeaux et CNRS UMR 5234 Microbiologie Fondamentale et Pathogénicité, Universite de Bordeaux 2, Bordeaux, France
    AIDS Res Hum Retroviruses 28:1798-802. 2012
    ..In naive patients, DRMs were observed with percentages ranging from 4% to 9% depending on drug classes. In treated patients at failure, numerous DRMs could be noted that induce actual or potential resistance to major NRTIs and NNRTIs...
  36. pmc Mechanism of dissociative inhibition of HIV protease and its autoprocessing from a precursor
    Jane M Sayer
    Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, DHHS, Bethesda, MD 20892, USA
    J Mol Biol 422:230-44. 2012
    ..However, its failure to recognize drug-resistant clinical mutants of PR may be beneficial to monitor the selection of mutations in this region under drug pressure...
  37. pmc Minor protease inhibitor mutations at baseline do not increase the risk for a virological failure in HIV-1 subtype B infected patients
    Alexandra U Scherrer
    Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
    PLoS ONE 7:e37983. 2012
    ..Previous studies showed that their presence impairs the antiretroviral treatment (ART) response. Evaluating these findings in a larger cohort is essential...
  38. ncbi Transmitted HIV type 1 drug resistance in newly diagnosed Cuban patients
    Liuber Y Machado
    AIDS Research Laboratory, Carretera Tapaste y Autopista Nacional, San José de las Lajas, Mayabeque 32700, Cuba
    AIDS Res Hum Retroviruses 29:411-4. 2013
    ..The results of this study provide evidence of TDR in the Cuban seropositive population and suggest the necessity of making resistance assays before beginning antiretroviral therapy in HIV-1-infected patients in Cuba...
  39. pmc Genotypic testing for human immunodeficiency virus type 1 drug resistance
    Robert W Shafer
    Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, California 94305, USA
    Clin Microbiol Rev 15:247-77. 2002
    ..This review describes the genetic mechanisms of HIV-1 drug resistance and summarizes published data linking individual RT and protease mutations to in vitro and in vivo resistance to the currently available HIV drugs...
  40. ncbi An increase in viral replicative capacity drives the evolution of protease inhibitor-resistant human immunodeficiency virus type 1 in the absence of drugs
    Noortje M van Maarseveen
    Department of Virology, Eijkman Winkler Center, University Medical Center Utrecht, Utrecht, The Netherlands
    J Acquir Immune Defic Syndr 42:162-8. 2006
    ..In the case of these viruses, it is not so likely that higher fitness peaks are present within the sequence space, and therefore, these variants will persist in the absence of drug pressure...
  41. pmc Dynamics of preferential substrate recognition in HIV-1 protease: redefining the substrate envelope
    Aysegül Ozen
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA
    J Mol Biol 410:726-44. 2011
    ....
  42. ncbi Impact of baseline polymorphisms in RT and protease on outcome of highly active antiretroviral therapy in HIV-1-infected African patients
    A J Frater
    Jefferiss Research Trust Laboratories, Wright-Fleming Institute, Imperial College School of Medicine, St Mary's Hospital, London, UK
    AIDS 15:1493-502. 2001
    ..Non-B subtypes are fully sensitive to HAART and, accordingly, therapy should not be withheld from African patients for reasons of viral diversity...
  43. ncbi Evolution and predictors of HIV type-1 drug resistance in patients failing combination antiretroviral therapy in Italy
    Simona Di Giambenedetto
    Institute of Clinical Infectious Diseases, Catholic University, Rome, Italy
    Antivir Ther 14:359-69. 2009
    ..This study aimed to examine the evolution of genotypic drug resistance prevalence in treatment-failing patients in the multicentre, Italian, Antiretroviral Resistance Cohort Analysis (ARCA)...
  44. pmc Predicting tipranavir and darunavir resistance using genotypic, phenotypic, and virtual phenotypic resistance patterns: an independent cohort analysis of clinical isolates highly resistant to all other protease inhibitors
    Annie Talbot
    Clinique du Quartier Latin and Centre Hospitalier de l Université de Montréal, Montreal, Quebec, Canada
    Antimicrob Agents Chemother 54:2473-9. 2010
    ..Generally, GISs predict susceptibility to darunavir substantially better than they predict susceptibility to tipranavir...
  45. ncbi Conformational flexibility in the flap domains of ligand-free HIV protease
    Holly Heaslet
    Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Acta Crystallogr D Biol Crystallogr 63:866-75. 2007
    The crystal structures of wild-type HIV protease (HIV PR) in the absence of substrate or inhibitor in two related crystal forms at 1.4 and 2.15 A resolution are reported. In one crystal form HIV PR adopts an 'open' conformation with a 7...
  46. pmc A multifaceted analysis of HIV-1 protease multidrug resistance phenotypes
    Kathleen M Doherty
    Department of Chemistry, Wellesley College, MA 02481, USA
    BMC Bioinformatics 12:477. 2011
    ..Understanding the phenotypic and genotypic patterns responsible for multi-PI resistance is necessary for developing PIs that are active against clinically-relevant PI-resistant HIV-1 variants...
  47. pmc Human immunodeficiency virus type 1 protease-correlated cleavage site mutations enhance inhibitor resistance
    Madhavi Kolli
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation St, Worcester, MA 01605, USA
    J Virol 83:11027-42. 2009
    ..Thus, cleavage site mutations should be considered when assessing the level of PI resistance...
  48. pmc Predicting drug resistance of the HIV-1 protease using molecular interaction energy components
    Tingjun Hou
    Department of Chemistry and Biochemistry, University of California, La Jolla, San Diego, California 92093, USA
    Proteins 74:837-46. 2009
    ..We believe that MIEC-SVM and MIEC-PLS can help design new agents or combination of therapeutic regimens to counter HIV-1 protease resistant strains...
  49. ncbi Molecular dynamics simulations of 14 HIV protease mutants in complexes with indinavir
    Xianfeng Chen
    Department of Biology, Molecular Basis of Disease Program, Georgia State University, GA 30303, Atlanta, USA
    J Mol Model 10:373-81. 2004
    ..figure: see text]. Poincare map representation for WT protease-indinavir complex. The side chain of Tyr 59 showing the positions of hydrogen atoms...
  50. pmc HIV-1 protease substrate binding and product release pathways explored with coarse-grained molecular dynamics
    Joanna Trylska
    Interdisciplinary Centre for Mathematical and Computational Modeling, University of Warsaw, Warsaw, Poland
    Biophys J 92:4179-87. 2007
    ..Moreover, the active site residues and the flap tips move in phase with the peptide. We suggest some mechanistic principles for how the flexibility of the protein may be involved in ligand binding and release...
  51. ncbi Binding pathways of ligands to HIV-1 protease: coarse-grained and atomistic simulations
    Chia en A Chang
    Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093, USA
    Chem Biol Drug Des 69:5-13. 2007
    ..Simulations allow us to efficiently study the ligand binding processes and may help those who study drug discovery to find optimal association pathways and to design those ligands with the best binding kinetics...
  52. ncbi Coarse-grained molecular dynamics of ligands binding into protein: The case of HIV-1 protease inhibitors
    Dechang Li
    Department of Engineering Mechanics, School of Aerospace, Tsinghua University, Beijing 100084, China
    J Chem Phys 130:215102. 2009
    ..The interaction strength between the PR and various inhibitors is also analyzed by atomistic molecular mechanics and Poisson-Boltzmann solvation area method...
  53. ncbi Relationships between structure and interaction kinetics for HIV-1 protease inhibitors
    Per Olof Markgren
    Department of Biochemistry, Uppsala University, BMC, SE 751 23 Uppsala, Sweden
    J Med Chem 45:5430-9. 2002
    ..The present approach thus provides a new tool for structure-interaction kinetic analysis and drug discovery...
  54. ncbi Closing of the flaps of HIV-1 protease induced by substrate binding: a model of a flap closing mechanism in retroviral aspartic proteases
    Gergely Toth
    Locus Pharmaceuticals, Four Valley Square, 512 Township Line Road, Blue Bell, Pennsylvania 19422, USA
    Biochemistry 45:6606-14. 2006
    ..The flap closing mechanism described in HIV-1 PR is proposed to be a general model for flap closing in retroviral aspartic proteases...
  55. pmc Computational study of protein specificity: the molecular basis of HIV-1 protease drug resistance
    W Wang
    Graduate Group in Biophysics, and Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143, USA
    Proc Natl Acad Sci U S A 98:14937-42. 2001
    ..We have evaluated the free energy contribution of each residue in the HIV protease in binding to one of its substrates and to the five FDA-approved protease drugs...
  56. ncbi HIV-1 protease cleavage site prediction based on amino acid property
    Bing Niu
    School of Materials Science and Engineering, Shanghai University, 149 Yan Chang Road, Shanghai 200072, People s Republic of China
    J Comput Chem 30:33-9. 2009
    Knowledge of the polyprotein cleavage sites by HIV protease will refine our understanding of its specificity, and the information thus acquired is useful for designing specific and efficient HIV protease inhibitors...
  57. ncbi Persistence of HIV-1 variants with multiple protease inhibitor (PI)-resistance mutations in the absence of PI therapy can be explained by compensatory fixation
    Noortje M van Maarseveen
    Eijkman Winkler Center, Department of Virology, University Medical Center Utrecht, Utrecht, The Netherlands
    J Infect Dis 195:399-409. 2007
    ..To investigate the mechanism explaining the persistence of human immunodeficiency virus (HIV) type 1 variants with multiple protease inhibitor (PI)-resistance mutations in the absence of PI therapy...
  58. pmc Full-length HIV-1 Gag determines protease inhibitor susceptibility within in vitro assays
    Ravindra K Gupta
    MRC Centre for Medical Molecular Virology, University College London, Windeyer Institute, London, UK
    AIDS 24:1651-5. 2010
    ..We wished to assess the contribution of full-length Gag to protease inhibitor susceptibility in viruses unexposed to protease inhibitors, in particular from the most common HIV-1 subtypes, namely subtype A and C...
  59. pmc Multiple, linked human immunodeficiency virus type 1 drug resistance mutations in treatment-experienced patients are missed by standard genotype analysis
    Sarah Palmer
    HIV Drug Resistance Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
    J Clin Microbiol 43:406-13. 2005
    ..In addition to having greater sensitivity, single-genome sequencing identifies linked mutations that confer high-level drug resistance. Such linkage cannot be detected by standard genotype analysis...
  60. pmc Human immunodeficiency virus type 1 protease cleavage site mutations associated with protease inhibitor cross-resistance selected by indinavir, ritonavir, and/or saquinavir
    H C Côté
    British Columbia Centre for Excellence in HIV AIDS, St Paul s Hospital, Vancouver, British Columbia, Canada V6Z 1Y6
    J Virol 75:589-94. 2001
    ..An A-->V substitution at the P2 position of the NC/p1 and NC/TFP cleavage sites was the most common (29%) change selected by the PIs used in this study...
  61. pmc Fitness landscape of human immunodeficiency virus type 1 protease quasispecies
    Guerau Fernandez
    Fundacio irsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autonoma de Barcelona, 08916 Badalona, Barcelona, Spain
    J Virol 81:2485-96. 2007
    ....
  62. ncbi Genotypic and phenotypic analyses of human immunodeficiency virus type 1 in antiretroviral drug-naive Nigerian patients
    Simon M Agwale
    Gede AIDS and Infectious Diseases Research Institute, Maitama, PMB 5158 Wuse, Abuja, Nigeria
    AIDS Res Hum Retroviruses 22:22-6. 2006
    ..Two isolates showed slightly reduced susceptibility to one or two of the five PIs assessed (ritonavir and ritonavir/nelfinavir) and all 18 viruses were susceptible to all NRTIs and NNRTIs analyzed...
  63. ncbi Cleavage of eIF4G by HIV-1 protease: effects on translation
    Celia Perales
    Centro de Biologi a Molecular Severo Ochoa, Facultad de Ciencias, Universidad Autonoma CSIC, Cantoblanco 28049, Madrid, Spain
    FEBS Lett 533:89-94. 2003
    ..Our present findings suggest that eIF4GI intactness is necessary to maintain cap-dependent translation, not only in cell-free systems but also in mammalian cells...
  64. pmc Evaluating the potency of HIV-1 protease drugs to combat resistance
    Tingjun Hou
    Department of Chemistry and Biochemistry, Center for Theoretical Biological Physics, University of California at San Diego, La Jolla, California 92093 0359, USA
    Proteins 71:1163-74. 2008
    ..We analyzed the conservation of each protease residue and also compared the interaction between the HIV protease and individual residues of the drugs and substrates...
  65. ncbi Transmission of HIV drug resistance and non-B subtype distribution in the Spanish cohort of antiretroviral treatment naïve HIV-infected individuals (CoRIS)
    Federico Garcia
    Microbiology Department, Hospital Universitario San Cecilio, Granada, Spain
    Antiviral Res 91:150-3. 2011
    ..Up to November 2008, a total of 683 FASTA format sequences, encoding the HIV protease and reverse transcriptase (RT) derived from plasma samples at entry into the cohort, had been obtained for ..
  66. ncbi Predictors of HIV drug-resistance mutations in a large antiretroviral-naive cohort initiating triple antiretroviral therapy
    P Richard Harrigan
    British Columbia Centre for Excellence in HIV AIDS, and Department of Medicine, University of British Columbia, Vancouver, Canada
    J Infect Dis 191:339-47. 2005
    ....
  67. pmc Accessory mutations maintain stability in drug-resistant HIV-1 protease
    Max W Chang
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Mol Biol 410:756-60. 2011
    ..Resistance mutations were also found to decrease the activity of HIV protease near neutral pH values, while incorporating stabilizing mutations improved the enzyme's pH tolerance...
  68. ncbi Evidence for positive epistasis in HIV-1
    Sebastian Bonhoeffer
    Ecology and Evolution, ETH Zurich, ETH Zentrum NW, CH 8092 Zurich, Switzerland
    Science 306:1547-50. 2004
    ..Using amino acid sequence data and fitness values from 9466 human immunodeficiency virus 1 (HIV-1) isolates, we find in contrast to these theories strong statistical evidence for a predominance of positive epistasis in HIV-1...
  69. pmc Origin of human immunodeficiency virus type 1 quasispecies emerging after antiretroviral treatment interruption in patients with therapeutic failure
    Gustavo H Kijak
    National Reference Center for AIDS, Department of Microbiology, School of Medicine, University of Buenos Aires, Argentina
    J Virol 76:7000-9. 2002
    ..This study demonstrates the important role that the reemergence of quasispecies plays in HIV-1 population dynamics and points out the difficulties that may be found when recycling ARV therapies with patients with treatment failure...
  70. pmc Mechanism of substrate recognition by drug-resistant human immunodeficiency virus type 1 protease variants revealed by a novel structural intermediate
    Moses Prabu-Jeyabalan
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation St, Worcester, MA 01605, USA
    J Virol 80:3607-16. 2006
    ..Thus, a plausible structural model for the adaptability of HIV-1 protease to recognize substrates in the presence of drug-resistant mutations has been proposed...
  71. ncbi A human immunodeficiency virus type 1 protease biosensor assay using bioluminescence resonance energy transfer
    Kimberly Hu
    HIV 1 RNA Trafficking Laboratory, Sir Mortimer B Davis Jewish General Hospital, 3999 Cote Ste Catherine Road, Montreal, Que, Canada H3T 1E2
    J Virol Methods 128:93-103. 2005
    ..This PR BRET2 biosensor assay can be adapted for high throughput screening of new HIV-1 PR inhibitors. It can be employed to screen for antiviral compounds that also target the proteases of other viruses...
  72. pmc Resistance-associated loss of viral fitness in human immunodeficiency virus type 1: phenotypic analysis of protease and gag coevolution in protease inhibitor-treated patients
    F Mammano
    Unité d Oncologie Virale, Departement SIDA et Retrovirus, Institut Pasteur, Paris, France
    J Virol 72:7632-7. 1998
    ..Our data provide clear evidence of the interplay between resistance and fitness in HIV-1 evolution in patients treated with protease inhibitors...
  73. pmc Efficient molecular docking of NMR structures: application to HIV-1 protease
    Sheng You Huang
    Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA
    Protein Sci 16:43-51. 2007
    ..The success of ensemble docking of the NMR structures suggests an efficient alternative method for standard single docking of crystal structures and for considering protein flexibility...
  74. pmc Polymorphism of the human immunodeficiency virus type 2 (HIV-2) protease gene and selection of drug resistance mutations in HIV-2-infected patients treated with protease inhibitors
    F Damond
    Hopital Bichat Claude Bernard, Paris, France
    J Clin Microbiol 43:484-7. 2005
    ..Substitutions selected under treatment were observed at positions corresponding to HIV-1 resistance mutations as well as at positions of currently unknown impact on HIV-1...
  75. pmc Distinguishing functional amino acid covariation from background linkage disequilibrium in HIV protease and reverse transcriptase
    Qi Wang
    Center for Computational Biology, Molecular Biology Institute, Institute for Genomics and Proteomics, University of California at Los Angeles, Los Angeles, United States of America
    PLoS ONE 2:e814. 2007
    ..Moreover, the specific set of (A,A) interaction pairs was reproducible in different drug treatment studies, and vanished in untreated HIV samples. The (S,S) covariation curves measured a low but detectable level of background LD in HIV...
  76. ncbi Compensatory mutations at the HIV cleavage sites p7/p1 and p1/p6-gag in therapy-naive and therapy-experienced patients
    Jens Verheyen
    Institute of Virology, University of Cologne, Cologne, Germany
    Antivir Ther 11:879-87. 2006
    ..Protease (PR) cleavage site (CS) mutations could compensate for impaired replication capacity of drug-resistant viruses...
  77. pmc Polymorphism and drug-selected mutations in the protease gene of human immunodeficiency virus type 2 from patients living in Southern France
    P Colson
    Laboratoire de Bacteriologie virologie, Centre Hospitalo Universitaire Timone et CNRS UMR 6020 IFR48, Universite de la Mediterranee, Marseilles, France
    J Clin Microbiol 42:570-7. 2004
    ..In conclusion, the present study revealed that HIV-2 strains harbor specific patterns of natural polymorphism and resistance...
  78. ncbi HIV-1 subtypes in Spain: a retrospective analysis from 1995 to 2003
    E Lospitao
    Infectious Diseases Service, Hospital Carlos III, Madrid, Spain
    HIV Med 6:313-20. 2005
    ..To perform a retrospective analysis of all HIV-1 non-B variants circulating in Spain from 1995 to 2003 and extend their virological characterization...
  79. ncbi Algorithms for the interpretation of HIV-1 genotypic drug resistance information
    Jurgen Vercauteren
    Clinical and Epidemiological Virology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, 3000 Leuven, Belgium
    Antiviral Res 71:335-42. 2006
    ..Successful therapy heavily relies on the expertise of the clinician...
  80. pmc Distribution of human immunodeficiency virus type 1 protease and reverse transcriptase mutation patterns in 4,183 persons undergoing genotypic resistance testing
    Soo Yon Rhee
    Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, California, USA
    Antimicrob Agents Chemother 48:3122-6. 2004
    ..Characterization of the phenotypic and clinical significance of these common patterns may lead to improved treatment recommendations for a large proportion of patients for whom antiretroviral therapy is failing...
  81. ncbi Molecular dynamics investigation on a series of HIV protease inhibitors: assessing the performance of MM-PBSA and MM-GBSA approaches
    Hemant Kumar Srivastava
    Centre for Molecular Modelling, CSIR Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500 607, India
    J Chem Inf Model 52:3088-98. 2012
    ..MD simulations (10 ns) for 14 HIV protease inhibitors have been carried out by using the Amber program...
  82. pmc An Escherichia coli expression assay and screen for human immunodeficiency virus protease variants with decreased susceptibility to indinavir
    L Melnick
    Sepracor Inc, Marlborough, Massachusetts 01752, USA
    Antimicrob Agents Chemother 42:3256-65. 1998
    ..We constructed a library of HIV protease variant genes containing dispersed mutations and, using the E...
  83. pmc A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism
    Monique Nijhuis
    Eijkman Winkler Center, Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, Netherlands
    PLoS Med 4:e36. 2007
    b>HIV protease inhibitor (PI) therapy results in the rapid selection of drug resistant viral variants harbouring one or two substitutions in the viral protease. To combat PI resistance development, two approaches have been developed...
  84. pmc HIV protease cleaves poly(A)-binding protein
    Enrique Alvarez
    Centro de Biologia Molecular Severo Ochoa CSIC UAM, Facultad de Ciencias, Universidad Autonoma, Cantoblanco, 28049 Madrid, Spain
    Biochem J 396:219-26. 2006
    ..An additional cleavage site located at position 410 was detected for HIV-2 protease. These findings indicate that some retroviruses may share with picornaviruses and caliciviruses the capacity to proteolyse PABP...
  85. ncbi A drug discovery platform: a simplified immunoassay for analyzing HIV protease activity
    Kuntida Kitidee
    Division of Clinical Immunology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, 50200, Thailand
    J Virol Methods 186:21-9. 2012
    Although numerous methods for the determination of HIV protease (HIV-PR) activity have been described, new high-throughput assays are required for clinical and pharmaceutical applications due to the occurrence of resistant strains...
  86. ncbi Proteolytic processing of HIV-1 protease precursor, kinetics and mechanism
    J M Louis
    Laboratory of Chemical Physics, NIDDK, National Institutes of Health, Bethesda, Maryland 20892 0580, USA
    J Biol Chem 274:23437-42. 1999
    ....
  87. ncbi Clinical validation of saquinavir/ritonavir genotypic resistance score in protease-inhibitor-experienced patients
    Anne Genevieve Marcelin
    Department of Virology, Pitie Salpftriere Hospital, AP HP, Universite Pierre et Marie Curie, Paris, France
    Antivir Ther 12:247-52. 2007
    ..To identify a genotypic score for resistance to saquinavir boosted with ritonavir (SQV/r; 1,000/100 mg twice daily)-based regimens in protease inhibitor (PI)-experienced patients...
  88. pmc Noninvasive high-throughput single-cell analysis of HIV protease activity using ratiometric flow cytometry
    Rok Gaber
    Laboratory of Biotechnology, National Institute of Chemistry, Ljubljana 1000, Slovenia
    Sensors (Basel) 13:16330-46. 2013
    ..virus infection/ acquired immunodeficiency syndrome (HIV/AIDS) epidemic, ongoing development of novel HIV protease inhibitors is required...
  89. pmc Drug resistance in HIV-1 protease: Flexibility-assisted mechanism of compensatory mutations
    Stefano Piana
    Laboratory of Inorganic Chemistry, ETH Hönggerberg HCI, Zurich, Switzerland
    Protein Sci 11:2393-402. 2002
    ..We anticipate that this "flexibility-assisted" mechanism might be effective in the vast majority of compensatory mutations, which do not change the electrostatic properties of the enzyme...
  90. ncbi Surveillance of HIV drug resistance transmission in Iran: experience gained from a pilot study
    Seyed Mohsen Mousavi
    Department of Community Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Golgasht AVE, Tabriz, Iran
    Arch Virol 155:329-34. 2010
    ..Increasing the sample size and improving the yield from DBS would improve the accuracy of drug resistance surveillance and facilitate wider application of this methodology in Iran...
  91. ncbi Comparative studies on inhibitors of HIV protease: a target for drug design
    Sudha Jayaraman
    Bioinformatics Centre, MM, Banaras Hindu University, Varanasi 221 005, India
    In Silico Biol 8:427-47. 2008
    Bioinformatics tools are employed lately for in silico structure-function analysis of proteins. HIV protease inhibitors nelfinavir and tipranavir belong to the extended multi-ring systems...
  92. pmc Modulation of HIV-1 Gag NC/p1 cleavage efficiency affects protease inhibitor resistance and viral replicative capacity
    Noortje M van Maarseveen
    Dept of Medical Microbiology, Virology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
    Retrovirology 9:29. 2012
    ....
  93. pmc Catalytic efficiency and vitality of HIV-1 proteases from African viral subtypes
    A Velazquez-Campoy
    Department of Biology, The Johns Hopkins University, Baltimore, MD 21218, USA
    Proc Natl Acad Sci U S A 98:6062-7. 2001
    ..5 and 5. These results point to a higher biochemical fitness of the A and C proteases in the presence of existing inhibitors...
  94. ncbi HIV-2 protease sequences of subtypes A and B harbor multiple mutations associated with protease inhibitor resistance in HIV-1
    Danuta Pieniazek
    HIV and Retrovirology Branch and the Office of the Director, Division of AIDS, STD, and TB Laboratory Research, National Center for Infectious Diseases, Atlanta, Georgia, USA
    AIDS 18:495-502. 2004
    ..HIV-1 protease inhibitors (PI) have been used for treating HIV-2-infected persons but little is known about amino acid mutations associated with PI resistance in HIV-2 and whether they are similar to those seen in HIV-1...
  95. ncbi In vitro and in vivo effects of HIV protease inhibitors on apoptosis
    A D Badley
    Translational, Immunology and Biodefense Program, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
    Cell Death Differ 12:924-31. 2005
    Development of potent inhibitors of HIV protease has revolutionized the treatment of HIV infection...
  96. ncbi Crystallization of a non-B and a B mutant HIV protease
    Mario Sanches
    Crystallography Group, Physics Department, USP, Sao Carlos, SP, Brazil
    Acta Crystallogr D Biol Crystallogr 60:1625-7. 2004
    ..The crystals of subtype F HIV protease are, to the best of the authors' knowledge, the first protein crystals obtained for a non-B HIV protease.
  97. pmc A potent human immunodeficiency virus type 1 protease inhibitor, UIC-94003 (TMC-126), and selection of a novel (A28S) mutation in the protease active site
    Kazuhisa Yoshimura
    Experimental Retrovirology Section, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Virol 76:1349-58. 2002
    ....
  98. ncbi Resistance to HIV protease inhibitors: a comparison of enzyme inhibition and antiviral potency
    R M Klabe
    Department of Virology, Experimental Station, DuPont Merck Pharmaceutical Company, Wilmington, Delaware 19880 0336, USA
    Biochemistry 37:8735-42. 1998
    ..Therefore, our data suggest that measurements of enzyme inhibition with mutant proteases may be poorly predictive of the antiviral effect in resistant viruses even when mutations are restricted to the protease gene...
  99. ncbi Effect of genotypic resistance on the virological response to highly active antiretroviral therapy in cerebrospinal fluid
    P Cinque
    Division of Infectious Diseases, San Raffaele Hospital, 20127 Milan, Italy
    AIDS Res Hum Retroviruses 17:377-83. 2001
    ..Most of these cases were not associated with the presence of resistant HIV strains in the CSF...
  100. pmc Cell-based fluorescence assay for human immunodeficiency virus type 1 protease activity
    K Lindsten
    Microbiology and Tumor Biology Center, Karolinska Institutet, S-171 77 Stockholm, Sweden
    Antimicrob Agents Chemother 45:2616-22. 2001
    ..The precursor provides a convenient and noninfectious model for high-throughput screenings of substances that can interfere with the activity of the protease in living cells...
  101. ncbi Design, synthesis, evaluation, and crystallographic-based structural studies of HIV-1 protease inhibitors with reduced response to the V82A mutation
    Jose C Clemente
    Department of Biochemistry and Molecular Biology, University of Florida College of Medicine, Gainesville, Florida 32610, USA
    J Med Chem 51:852-60. 2008
    ..Moreover, scrutiny of the X-ray structure suggests that the ring of the Cha side chain might be in a boat rather than in the chair conformation, a result supported by molecular dynamics simulations...

Research Grants65

  1. DESIGN AND SYNTHESIS OF NONPEPTIDE PROTEASE INHIBITORS
    Arun K Ghosh; Fiscal Year: 2010
    ..Based upon our high resolution X-ray crystal structures of darunavir-bound HIV protease and a number of other protein-ligand structures, we have envisioned a number of intriguing design concepts and ..
  2. DEVELOPMENT OF LIGAND ASSISTED ASYMMETRIC SYNTHESES
    Arun Ghosh; Fiscal Year: 2001
    ..Besides the broad range of scope and generality, this line of research will provide excellent opportunities to teach and train graduate and undergraduate students in the laboratory. ..
  3. Drug Resistance in Non-Subtype B HIV-1
    Susan Eshleman; Fiscal Year: 2005
    ..abstract_text> ..
  4. Public HIV Drug Resistance Database
    ROBERT WILLIAM SHAFER; Fiscal Year: 2010
    ..UCL is on the forefront of research into the problem of transmitted drug resistance and Oxford University is on the forefront of research on virus evolution and population genetics. ..
  5. Identification of Mulit-Drug Resistant HIV-1 Isolates
    Robert Shafer; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  6. Fitness of Enfuvirtide-(T-20)-Resistant HIV-1
    Daniel Kuritzkes; Fiscal Year: 2006
    ..Results of these studies will provide a deeper understanding of the molecular, virologic, and clinical consequences ofT-20 resistance, and may help guide the use of T-20 in salvage therapy. ..
  7. Design and Synthesis of HIV-1 Protease Inhibitors
    AMOS SMITH; Fiscal Year: 2004
    ....
  8. SYNTHESIS OF CHLOROPEPTINS, GP120 CD4 BINDING INHIBITORS
    AMOS SMITH; Fiscal Year: 2001
    ..abstract_text> ..
  9. SYNTHESIS OF SPONGISTATIN ANTITUMOR AGENTS
    AMOS SMITH; Fiscal Year: 2007
    ..abstract_text> ..
  10. NMR systems : 2 Bruker Avance 500 Consoles
    AMOS SMITH; Fiscal Year: 2006
    ..The areas of public health research include, among others, cancer, infectious diseases, neurodegenerative diseases such as Alzheimer's disease, and heart and cardiovascular disease. [unreadable] [unreadable] [unreadable]..
  11. HIV-1 THERAPEUTICS AND DRUG RESISTANCE
    Daniel R Kuritzkes; Fiscal Year: 2010
    ..This research program provides a framework within which the applicant can mentor beginning clinical investigators in patient-oriented research focused on critical issues in HIV-1 medicine. ..
  12. HIV-1 resistance to nucleoside analogues
    Daniel Kuritzkes; Fiscal Year: 2004
    ..Better understanding of the virologic, genetic, and biochemical aspects of AZT/3TC dual resistance will help direct therapy and may lead to better therapeutic strategies in the future. ..
  13. HIV-Associated Dementia and the Urokinase Plasminogen Activation System
    Paola Cinque; Fiscal Year: 2007
    ..Although expected findings will be only correlative, these might represent the basis for functional studies in other models and evaluation of new therapeutic strategies. [unreadable] [unreadable] [unreadable]..
  14. Characterization of a single cycle SIV vaccine candidate
    Ronald Swanstrom; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  15. International Clinical Trials Unit
    John Bartlett; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  16. MR imaging of myeloperoxidase activity
    Ralph Weissleder; Fiscal Year: 2007
    ..The ultimate goal of this research is to develop clinically useful imaging tools for the molecular assessment of atherosclerosis in vivo, which are currently limited. [unreadable] [unreadable] [unreadable]..
  17. Phase I Application: Cleaning of Single Cell DNA Measurements In-Silico
    Matthew Rabinowitz; Fiscal Year: 2007
    ..This reliable genotyping data is absolutely critical for the task of predicting susceptibilities to various disease phenotypes. [unreadable] [unreadable] [unreadable]..
  18. HIV Drug Resistance During HAART in Adolescents
    Deborah Persaud; Fiscal Year: 2007
    ..The clinical specimens and analytic resources available within the ATN provide a unique opportunity to study HIV pathogenesis in infected adolescents. ..
  19. Enhancing HIV Prevention Among High-Risk HIV+ Men
    Kenneth Mayer; Fiscal Year: 2007
    ..Participants will then be followed every three months for one year, integrating PCM and/or prevention booster sessions to their HIV care visits. ..
  20. Implications of HIV in Low HCV Clearance in Chinese IDUs
    Xiao Fang Yu; Fiscal Year: 2007
    ..The results of these studies should provide further insight into the mechanism of HCV clearance and the development of immunity which are critical for the development of effective vaccine and new treatment strategies. ..
  21. Novel algorithms and organisms for Onto-Tools
    Sorin Draghici; Fiscal Year: 2007
    ..The enhanced Onto-Tools will continue to be freely available. Onto-Analyzer and the software evolution tools developed under this proposal will be made freely available to the research community, as well. ..
  22. Predictors of Immunologic Long-term Non-Progression in Children with HIV
    Jintanat Ananworanich; Fiscal Year: 2010
    ..This will be important in deciding when to treat children with antiretroviral therapy. ..
  23. HIV-1 chemoprophylaxis and archived drug resistance in infants
    Deborah Persaud; Fiscal Year: 2010
    ....
  24. A Systematic Approach to the Chemical Synthesis of G-Protein Coupled Receptors
    Stephen Kent; Fiscal Year: 2009
    ....
  25. True prevalence of pre-existing reverse transcriptase inhibitor resistance in tre
    Rafael Campo; Fiscal Year: 2008
    ..Most importantly, unrecognized resistance might impair the efficacy of antiretroviral therapy, and its timely identification could lead to better treatment outcomes. [unreadable] [unreadable] [unreadable]..
  26. HIV Vaccines on Latent Reservoirs in Young Adults on HAART
    Deborah Persaud; Fiscal Year: 2008
    ..Clinical specimens and analytic resources from VRC and PACTG provide a unique opportunity to study pathogenesis of viral reservoirs in HIV-1 infected individuals. [unreadable] [unreadable] [unreadable]..
  27. Role of Cul5 E3 ubiquitin ligase in HIV Vif function
    Xiao Fang Yu; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  28. Procaspase 8 Activation by HIV Protease
    Andrew Badley; Fiscal Year: 2008
    ..It has long been recognized that one HIV protein, HIV protease, is intrinsically cytotoxic as its expression causes the death of bacteria, yeast, and mammalian cells, however ..
  29. Characterization of CNS-Compartmentalized env Genes
    Ronald Swanstrom; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  30. ENZYMES IN ORGANIC SYNTHESIS
    Chi Huey Wong; Fiscal Year: 2008
    ..Significant contributions in the areas of biomedicine and synthetic organic chemistry are expected. These developments may facilitate the discovery and development of new therapeutic agents. ..
  31. BACKBONE EFFECTS ON PROTEIN STABILITY AND FOLDING
    Philip E Dawson; Fiscal Year: 2010
    ..abstract_text> ..
  32. Novel Statistical Methods for Improving the Prediction of HIV-1 Response to ART a
    Matthew Rabinowitz; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  33. RNA as a Target for Intervention
    William Greenberg; Fiscal Year: 2007
    ....
  34. ADULT AIDS CLINICAL TRIALS UNIT
    John Bartlett; Fiscal Year: 2006
    ..The applicants anticipate that Duke will continue as an efficient, cost-effective ACTU that contributes to the ACTG scientific agenda. ..
  35. HIV-1 RT dimerization as an antiviral target
    Nicolas Sluis Cremer; Fiscal Year: 2005
    ..abstract_text> ..
  36. A cell-based assay to measure HCV drug susceptibility
    Neil Parkin; Fiscal Year: 2004
    ....
  37. Structure-Based Design of Bacterial GTPase Inhibitors
    Mark Shenderovich; Fiscal Year: 2004
    ..abstract_text> ..
  38. MR IMAGING OF GENE EXPRESSION
    Ralph Weissleder; Fiscal Year: 2004
    ..The long-term goal of this research is to extend the capabilities of MR and apply it to in vivo imaging of gene expression. ..
  39. A Model System for HIV Multi-Drug Therapy Design
    Chen Chen Kan; Fiscal Year: 2003
    Clinically effective inhibitors of the HIV protease are generally considered major successes in structure-based drug design. Despite these successes, a cure for AIDS has remained elusive...
  40. BEHAVIORAL AND VIROLOGIC FEATURES OF HIV+ IDUS IN CHINA
    Xiao Fang Yu; Fiscal Year: 2002
    ..These aims will be carried out in Guangxi Province through a longitudinal investigation of 600 drug users about whom demographic, social, and drug use information will be collected and analyzed. ..
  41. INHIBITION OF HHV 8 GENE EXPRESSION BY RIBOZYMES
    Thomas Campbell; Fiscal Year: 2001
    ....
  42. EVALUATION OF HIV GAG DNA VACCINE TO MAX T HELPER/CTL
    Xiao Fang Yu; Fiscal Year: 2001
    ..C) Combination studies by using DNA vectors identified from this specific aim with DNA vectors identified from specific aim 1. ..
  43. LCDIO FOR LYMPH NODE MR IMAGING
    Ralph Weissleder; Fiscal Year: 2001
    ..abstract_text> ..
  44. STRUCTURE/FUNCTION OF HIV1 CAPSID/CYCLOPHILIN COMPLEX
    Wesley Sundquist; Fiscal Year: 2001
    ..Finally, genetic analysis of mutants of CA in an HIV provirus will be used to test models that arise from the CA and CA-cyclophilin structures. ..
  45. Diffuse optical tomography system for molecular imaging
    Ralph Weissleder; Fiscal Year: 2005
    ....
  46. Phylogenetics and recombination
    Keith Crandall; Fiscal Year: 2005
    ..It will also provide the first comprehensive assessment of the impact of recombination in shaping the current genetic diversity of HIV-1 using statistically validated techniques. ..
  47. Drug susceptibility assay for non-subtypr B HIV-1
    Neil Parkin; Fiscal Year: 2006
    ....
  48. VIRAL & HOST FACTORS ON HIV TRANSMISSION/PATHOGENESIS
    Xiao Fang Yu; Fiscal Year: 2004
    ..2) To study the influence of host genetic factors on HIV transmission and disease progression. The results of these studies should provide further insight into the mechanism of HIV transmission and pathogenesis. ..
  49. Integrating, Validating & Applying Pharmacogenetic Data
    Matthew Rabinowitz; Fiscal Year: 2006
    ..The Gene Security Network stands to significantly reduce this burden and greatly improve the speed and accuracy of clinical decision-making. [unreadable] [unreadable] [unreadable]..
  50. Significance of Oral KS in an African Setting
    Thomas Campbell; Fiscal Year: 2006
    ..It is expected that the results of these studies will provide useful information to programs for introduction of contemporary antiretroviral treatment in resource-limited areas of Africa. [unreadable] [unreadable]..
  51. Structural Biology of HIV Assembly, Budding, and Entry
    Wesley Sundquist; Fiscal Year: 2006
    ..In summary, our Program will provide significant insights into how the HIV virion functions as a machine that can enter and exit cells, and how these processes can be inhibited. ..
  52. Hepatitis C Microarrays to Detect Drug Resistance
    Michael Kozal; Fiscal Year: 2006
    ..If successful this project will create a tool that can rapidly and accurately provide the sequence of HCV genes that encode drug targets and facilitate the investigations into the genetic determinants of HCV drug resistance. ..
  53. Novel Adenovirus Vaccine Vectors for HIV/SIV
    Dan H Barouch; Fiscal Year: 2010
    ..abstract_text> ..
  54. Molecular Modulators of HCV Replication
    Neerja Kaushik Basu; Fiscal Year: 2007
    ..This will enable us to understand, at the molecular level, the replication process of hepatitis C virus and will further facilitate the development of effective drugs/inhibitors against HCV. ..
  55. EFFECTORS AND IINHIBITORS OF SARS VIRUS POLYMERASE
    Neerja Kaushik Basu; Fiscal Year: 2006
    ..Further, analysis of the sensitivity of the SARS-CoV RdRp towards a panel of known and novel inhibitors of polymerases will provide new leads in the quest for specific antiviral agents against the SARS-CoV RdRp. ..
  56. Targeting Acute HIV
    Christopher Pilcher; Fiscal Year: 2007
    ..Perform detailed cost effectiveness modeling in order to optimize acute HIV-centered efforts at HIV prevention. ..
  57. BIOCHEMISTRY OF HEPATITIS C VIRUS REPLICASE
    Neerja Kaushik Basu; Fiscal Year: 2003
    ..Aim 2: To elucidate the catalytic roles of specific amino acid residues in the polymerase function. Aim 3: To determine protein-protein interactions between HCV replicase and other nonstructural viral proteins. ..
  58. Statistical and Computational Methods for Systematically Mining the SNP and Gene
    Zhenqiu Liu; Fiscal Year: 2008
    ..We hope our researches have the impact of encouraging more people to contribute to this challenging problem. [unreadable] [unreadable] [unreadable]..
  59. Augmentation of DNA Vaccine-Elicited Immunity to HIV/SIV
    DAN BAROUCH; Fiscal Year: 2008
    ..The long-term objectives of these studies are to develop novel vaccine regimens that recruit APCs to the site of inoculation in animal models and to consider advancing the most promising strategies into clinical trials. ..
  60. CYTOREDUCTIVE CHEMOTHERAPY TARGETING HIV RESERVOIRS
    Christopher Pilcher; Fiscal Year: 2004
    ..the PI with supervised laboratory experiences and didactic training in addition to a closely supervised clinical research experience, leading to R01 submission and establishment of the PI as an independent investigator ..
  61. Epidemiology of HIV-1/HIV-2 Dual Infection
    Geoffrey Gottlieb; Fiscal Year: 2005
    ....
  62. Cytokine-Augmented DNA Vaccine-Elicited Immunity to HIV
    DAN BAROUCH; Fiscal Year: 2005
    ..Raphael Dolin, Dean for Clinical Programs, Harvard Medical School, will guide Dr. Barouch's development as an independent investigator. In addition, a committee of distinguished scientists will oversee his progress toward independence. ..
  63. Chimeric Adenovirus Vaccine Vectors for HIV/SIV
    DAN BAROUCH; Fiscal Year: 2005
    ..Within the two-year time frame of this award, sufficient data will be generated with candidate chimeric rAd vaccines to justify further vaccine/challenge studies in rhesus monkeys. ..