hiv fusion inhibitors

Summary

Summary: Inhibitors of the fusion of HIV to host cells, preventing viral entry. This includes compounds that block attachment of HIV ENVELOPE PROTEIN GP120 to CD4 RECEPTORS.

Top Publications

  1. ncbi Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America
    Jacob P Lalezari
    Quest Clinical Research, Mount Zion Hospital and the University of California, San Francisco, San Francisco 94115, USA
    N Engl J Med 348:2175-85. 2003
  2. pmc V3 determinants of HIV-1 escape from the CCR5 inhibitors Maraviroc and Vicriviroc
    Reem Berro
    Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10065, USA
    Virology 427:158-65. 2012
  3. pmc A maraviroc-resistant HIV-1 with narrow cross-resistance to other CCR5 antagonists depends on both N-terminal and extracellular loop domains of drug-bound CCR5
    John C Tilton
    Department of Microbiology, University of Pennsylvania, 301C Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104, USA
    J Virol 84:10863-76. 2010
  4. ncbi Pharmacokinetics of sifuvirtide, a novel anti-HIV-1 peptide, in monkeys and its inhibitory concentration in vitro
    Shu jia Dai
    Laboratory of Metabolism of Biotechnology Derived Drugs, Beijing Institute of Radiation Medicine, Beijing 100850, China
    Acta Pharmacol Sin 26:1274-80. 2005
  5. pmc Maraviroc for previously treated patients with R5 HIV-1 infection
    Roy M Gulick
    Weill Cornell Medical College, New York, NY 10065, USA
    N Engl J Med 359:1429-41. 2008
  6. pmc Resistance to CCR5 inhibitors caused by sequence changes in the fusion peptide of HIV-1 gp41
    Cleo G Anastassopoulou
    Department of Microbiology and Immunology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 106:5318-23. 2009
  7. pmc Synergistic efficacy of combination of enfuvirtide and sifuvirtide, the first- and next-generation HIV-fusion inhibitors
    Chungen Pan
    Lindsley F Kimball Research Institute, New York Blood Center, New York, NY 10065, USA
    AIDS 23:639-41. 2009
  8. pmc N-substituted pyrrole derivatives as novel human immunodeficiency virus type 1 entry inhibitors that interfere with the gp41 six-helix bundle formation and block virus fusion
    Shibo Jiang
    Lindsley F Kimball Research Institute, New York Blood Center, 310 E 67th St, New York, NY 10021, USA
    Antimicrob Agents Chemother 48:4349-59. 2004
  9. pmc Peptides in the treatment of AIDS
    Fred Naider
    Department of Chemistry, College of Staten Island of the City University of New York, Staten Island, New York 10314, USA
    Curr Opin Struct Biol 19:473-82. 2009
  10. ncbi Mechanisms of viral membrane fusion and its inhibition
    D M Eckert
    Howard Hughes Medical Institute, Whitehead Institute for Biomedical Research, Department of Biology, M I T, Cambridge, Massachusetts 02142, USA
    Annu Rev Biochem 70:777-810. 2001

Detail Information

Publications249 found, 100 shown here

  1. ncbi Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America
    Jacob P Lalezari
    Quest Clinical Research, Mount Zion Hospital and the University of California, San Francisco, San Francisco 94115, USA
    N Engl J Med 348:2175-85. 2003
    ..The T-20 vs. Optimized Regimen Only Study 1 (TORO 1) was a randomized, open-label, phase 3 study of enfuvirtide (T-20), a human immunodeficiency virus type 1 (HIV-1) fusion inhibitor...
  2. pmc V3 determinants of HIV-1 escape from the CCR5 inhibitors Maraviroc and Vicriviroc
    Reem Berro
    Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10065, USA
    Virology 427:158-65. 2012
    ..In summary, VVC and MVC trigger the evolution of distinct HIV-1 resistance patterns in V3...
  3. pmc A maraviroc-resistant HIV-1 with narrow cross-resistance to other CCR5 antagonists depends on both N-terminal and extracellular loop domains of drug-bound CCR5
    John C Tilton
    Department of Microbiology, University of Pennsylvania, 301C Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104, USA
    J Virol 84:10863-76. 2010
    ....
  4. ncbi Pharmacokinetics of sifuvirtide, a novel anti-HIV-1 peptide, in monkeys and its inhibitory concentration in vitro
    Shu jia Dai
    Laboratory of Metabolism of Biotechnology Derived Drugs, Beijing Institute of Radiation Medicine, Beijing 100850, China
    Acta Pharmacol Sin 26:1274-80. 2005
    ..To study the pharmacokinetics of sifuvirtide, a novel anti-human immunodeficiency virus (HIV) peptide, in monkeys and to compare the inhibitory concentrations of sifuvirtide and enfuvirtide on HIV-1-infected-cell fusion...
  5. pmc Maraviroc for previously treated patients with R5 HIV-1 infection
    Roy M Gulick
    Weill Cornell Medical College, New York, NY 10065, USA
    N Engl J Med 359:1429-41. 2008
    ..CC chemokine receptor 5 antagonists are a new class of antiretroviral agents...
  6. pmc Resistance to CCR5 inhibitors caused by sequence changes in the fusion peptide of HIV-1 gp41
    Cleo G Anastassopoulou
    Department of Microbiology and Immunology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 106:5318-23. 2009
    ..Together, the experimental results and theoretical model may help understand how HIV-1 uses CCR5 to enter target cells under various conditions...
  7. pmc Synergistic efficacy of combination of enfuvirtide and sifuvirtide, the first- and next-generation HIV-fusion inhibitors
    Chungen Pan
    Lindsley F Kimball Research Institute, New York Blood Center, New York, NY 10065, USA
    AIDS 23:639-41. 2009
    ..These findings suggest that application of enfuvirtide and sifuvirtide in combination may improve their efficacy and resistant profile, leading to a reduction of the dosage and frequency of drug use...
  8. pmc N-substituted pyrrole derivatives as novel human immunodeficiency virus type 1 entry inhibitors that interfere with the gp41 six-helix bundle formation and block virus fusion
    Shibo Jiang
    Lindsley F Kimball Research Institute, New York Blood Center, 310 E 67th St, New York, NY 10021, USA
    Antimicrob Agents Chemother 48:4349-59. 2004
    ..Therefore, NB-2 and NB-64 can be used as lead compounds toward designing and developing more potent small molecule HIV-1 fusion inhibitors targeting gp41...
  9. pmc Peptides in the treatment of AIDS
    Fred Naider
    Department of Chemistry, College of Staten Island of the City University of New York, Staten Island, New York 10314, USA
    Curr Opin Struct Biol 19:473-82. 2009
    ..Knowledge of the structural biology of gp41 allows the design of potent peptide inhibitors that prevent the virus from entering lymphocytes and macrophages. The design of such inhibitors is the subject of this review...
  10. ncbi Mechanisms of viral membrane fusion and its inhibition
    D M Eckert
    Howard Hughes Medical Institute, Whitehead Institute for Biomedical Research, Department of Biology, M I T, Cambridge, Massachusetts 02142, USA
    Annu Rev Biochem 70:777-810. 2001
    ..This mechanism of infectivity is likely utilized by a wide variety of enveloped viruses for which similar therapeutic interventions should be possible...
  11. pmc Susceptibility of HIV-1 subtypes B', CRF07_BC and CRF01_AE that are predominantly circulating in China to HIV-1 entry inhibitors
    Xiaoling Yu
    State Key Laboratory for Infection Disease Prevention and Control, National Center for AIDS STD Control and Prevention NCAIDS, Chinese Center for Disease Control and Prevention China CDC, Beijing, China
    PLoS ONE 6:e17605. 2011
    ..The B', CRF07_BC and CRF01_AE are the predominant HIV-1 subtypes in China. It is essential to determine their baseline susceptibility to HIV entry inhibitors before these drugs are used in China...
  12. pmc MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency
    Katrijn Grupping
    Virology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine of Antwerp, Antwerp, Belgium
    Retrovirology 9:36. 2012
    ..The miniCD4 proteins are a promising class of CD4bs inhibitors. Studying virus evolution under pressure of CD4bs inhibitors could provide insight on the gp120-CD4 interaction and viral entry...
  13. pmc Scaleable manufacture of HIV-1 entry inhibitor griffithsin and validation of its safety and efficacy as a topical microbicide component
    Barry R O'Keefe
    Molecular Targets Development Program, National Cancer Institute at Frederick, Frederick, MD 21702, USA
    Proc Natl Acad Sci U S A 106:6099-104. 2009
    ..Moreover, GRFT-P is potently active in preventing infection of cervical explants by HIV-1 and has no mitogenic activity on cultured human lymphocytes...
  14. ncbi Rescue of HIV-1 long-time archived X4 strains to escape maraviroc
    Franky Baatz
    Laboratory of Retrovirology, CRP Sante, Luxembourg, Luxembourg
    Antiviral Res 92:488-92. 2011
    ..Under maraviroc selective pressure, the early, no longer detectable X4 strains archived in PBMC were partially rescued to provide X4-determinants to the main circulating strain...
  15. ncbi Molecular interactions of CCR5 with major classes of small-molecule anti-HIV CCR5 antagonists
    Rama Kondru
    Department of Medicinal Chemistry, Roche Palo Alto, 3431 Hillview Avenue, Palo Alto, CA 94304, USA
    Mol Pharmacol 73:789-800. 2008
    ..The fully mapped binding pocket of CCR5 is being used for structure-based design and lead optimization of novel anti-HIV CCR5 inhibitors with improved potency and better resistance profile...
  16. ncbi T-1249 retains potent antiretroviral activity in patients who had experienced virological failure while on an enfuvirtide-containing treatment regimen
    Jacob P Lalezari
    Quest Clinical Research, San Francisco, California, USA
    J Infect Dis 191:1155-63. 2005
    ..T-1249 is a 39-amino acid synthetic peptide fusion inhibitor (FI) shown to preserve antiretroviral activity in vitro against human immunodeficiency virus (HIV) isolates that have decreased susceptibility to enfuvirtide (ENF)...
  17. ncbi Inhibition of HIV-1 by fusion inhibitors
    Dirk Eggink
    Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam CINIMA, Academic Medical Center of the University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands
    Curr Pharm Des 16:3716-28. 2010
    ..Here we discuss the development of fusion inhibitors, their mode of action and their potential for incorporation in future drug regimens...
  18. ncbi HIV entry inhibitors targeting gp41: from polypeptides to small-molecule compounds
    Shuwen Liu
    Viral Immunology Laboratory, Lindsley F Kimball Research Institute, New York Blood Center, New York, NY 10021, USA
    Curr Pharm Des 13:143-62. 2007
    ..The progress in development of those anti-HIV agents targeting gp41, from polypeptides to small-molecule compounds, is reviewed...
  19. ncbi Conserved residue Lys574 in the cavity of HIV-1 Gp41 coiled-coil domain is critical for six-helix bundle stability and virus entry
    Yuxian He
    Lindsley F Kimball Research Institute, New York Blood Center, New York, New York 10021, USA
    J Biol Chem 282:25631-9. 2007
    ..Collectively, these data suggest that conserved Lys574 plays a critical role in 6-HB formation and HIV-1 infectivity, and may serve as an important target for designing anti-HIV drugs...
  20. pmc Selection of T1249-resistant human immunodeficiency virus type 1 variants
    Dirk Eggink
    Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam, Academic Medical Center of the University of Amsterdam, P O Box 22700, 1100 DE Amsterdam, The Netherlands
    J Virol 82:6678-88. 2008
    ..Furthermore, substitutions at position 38 do not provide resistance to the third-generation inhibitor T2635, while substitution at positions 79 and 90 do, suggesting different resistance mechanisms...
  21. pmc Emergence and evolution of enfuvirtide resistance following long-term therapy involves heptad repeat 2 mutations within gp41
    L Xu
    Health Protection Agency Antiviral Suspectibility Reference Unit, Birmingham, UK
    Antimicrob Agents Chemother 49:1113-9. 2005
    ..We propose that this represents a possible secondary and/or compensatory mutation, particularly when it coexists with mutations at position 43 in HR-1...
  22. pmc A low-molecular-weight entry inhibitor of both CCR5- and CXCR4-tropic strains of human immunodeficiency virus type 1 targets a novel site on gp41
    Edward J Murray
    Antiviral Research Unit, IPC 424, Pfizer PGRD, Discovery Biology, Sandwich Laboratories, Sandwich, Kent CT13 9NJ, United Kingdom
    J Virol 84:7288-99. 2010
    ..The results highlight PF-68742 as a starting point for novel therapies against HIV-1 and provide new insights into models of Env-mediated fusion...
  23. pmc Mutations conferring resistance to human immunodeficiency virus type 1 fusion inhibitors are restricted by gp41 and Rev-responsive element functions
    Daisuke Nameki
    Laboratory of Virus Immunology, Institute for Virus Research, Kyoto University, 53 Shogoin Kawaramachi, Sakyoku, Kyoto 606 8507, Japan
    J Virol 79:764-70. 2005
    ..However, since this region also encoded the RRE, additional mutations were required to maintain viral replication. These results suggest that HIV fusion is one of the attractive targets for HIV chemotherapy...
  24. pmc Albumin-conjugated C34 peptide HIV-1 fusion inhibitor: equipotent to C34 and T-20 in vitro with sustained activity in SCID-hu Thy/Liv mice
    Cheryl A Stoddart
    Division of Experimental Medicine, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, California 94110, USA
    J Biol Chem 283:34045-52. 2008
    ....
  25. pmc Addition of a cholesterol group to an HIV-1 peptide fusion inhibitor dramatically increases its antiviral potency
    Paolo Ingallinella
    Merck Research Laboratories Peptide Center of Excellence and Department of Drug Metabolism, Istituto di Ricerche di Biologia Molecolare P Angeletti, 00040 Pomezia, Rome, Italy
    Proc Natl Acad Sci U S A 106:5801-6. 2009
    ..Because the fusion machinery targeted by C34-Chol is similar in several other enveloped viruses, we believe that these findings may be of general utility...
  26. ncbi Impact of the enfuvirtide resistance mutation N43D and the associated baseline polymorphism E137K on peptide sensitivity and six-helix bundle structure
    Xuefang Bai
    Protein Engineering Group and Virology Group, Trimeris, Inc, 3500 Paramount Parkway, Morrisville, North Carolina 27560, USA
    Biochemistry 47:6662-70. 2008
    ..These data form a framework for understanding the impact of resistance mutations on viral fitness and pathogenesis and provide a pathway for the development of novel fusion inhibitor peptides...
  27. pmc Impact of human immunodeficiency virus type 1 gp41 amino acid substitutions selected during enfuvirtide treatment on gp41 binding and antiviral potency of enfuvirtide in vitro
    M Mink
    Trimeris Inc, 3500 Paramount Parkway, Morrisville, NC 27560, USA
    J Virol 79:12447-54. 2005
    ....
  28. pmc Design of helical, oligomeric HIV-1 fusion inhibitor peptides with potent activity against enfuvirtide-resistant virus
    John J Dwyer
    Trimeris Inc, 3500 Paramount Parkway, Morrisville, NC 27560, USA
    Proc Natl Acad Sci U S A 104:12772-7. 2007
    ..The potent antiviral activity against resistant viruses, the difficulty in generating resistant virus, and the extended half-life in vivo make this class of fusion inhibitor peptide attractive for further development...
  29. pmc The role of the N-terminal segment of CCR5 in HIV-1 Env-mediated membrane fusion and the mechanism of virus adaptation to CCR5 lacking this segment
    Gregory B Melikyan
    Institute of Human Virology, University of Maryland School of Medicine, 725 W, Lombard St, Baltimore, MD 21201, USA
    Retrovirology 4:55. 2007
    ..However, mutations in gp120 adapt HIV-1 to grow on cells expressing the N-terminally truncated CCR5(Delta 18) (Platt et al., J. Virol. 2005, 79: 4357-68)...
  30. ncbi Design, synthesis, and biological activity of a novel series of 2,5-disubstituted furans/pyrroles as HIV-1 fusion inhibitors targeting gp41
    Shibo Jiang
    Lindsley F Kimball Research Institute, New York Blood Center, NY 10065, USA
    Bioorg Med Chem Lett 21:6895-8. 2011
    ....
  31. ncbi Current peptide HIV type-1 fusion inhibitors
    Wei Pang
    Key Laboratory of Animal Models and Human Diseases Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China
    Antivir Chem Chemother 20:1-18. 2009
    ..Some of these new compounds have great potential to be further developed as therapeutic agents. This article reviewed some recent developments of these peptides and the possible role in anti-HIV-1 therapy...
  32. pmc Early steps of HIV-1 fusion define the sensitivity to inhibitory peptides that block 6-helix bundle formation
    Kosuke Miyauchi
    Institute of Human Virology and Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA
    PLoS Pathog 5:e1000585. 2009
    ..We conclude that both the longevity of gp41 intermediates and the extent of irreversible conformational changes in Env upon CD4 binding determine the antiviral potency of C-peptides...
  33. ncbi Entry inhibitors in the treatment of HIV-1 infection
    John C Tilton
    Department of Microbiology, University of Pennsylvania, 301C Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104, United States
    Antiviral Res 85:91-100. 2010
    ..This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, Vol 85, issue 1, 2010...
  34. ncbi X-ray crystallographic study of an HIV-1 fusion inhibitor with the gp41 S138A substitution
    Tsuyoshi Watabe
    Kyoto University, Sakyo ku, Japan
    J Mol Biol 392:657-65. 2009
    ..Free-energy calculations suggest that the difference between the desolvation free energies of the C-HR-derived peptides with and without the S138A mutation dominates the observed difference in anti-HIV-1 activity...
  35. ncbi Naturally occurring resistance mutations to HIV-1 entry inhibitors in subtypes B, C, and CRF31_BC
    Leonardo Augusto Luvison Araújo
    Centro de Desenvolvimento Científico e Tecnológico CDCT, Fundação Estadual de Produção e Pesquisa em Saúde FEPPS, Porto Alegre, Brazil leonardo
    J Clin Virol 54:6-10. 2012
    ..Despite the importance of subtype C, which predominates globally, the majority of studies include only subtype B strains...
  36. pmc Mechanistic studies of a T20-dependent human immunodeficiency virus type 1 variant
    Chris Baldwin
    Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam, Academic Medical Center of the University of Amsterdam, P O Box 22700, 1100 DE Amsterdam, The Netherlands
    J Virol 82:7735-40. 2008
    ..In this study, we set out to critically test this mechanistic explanation with alternative effectors that may control the Env switch, including other fusion inhibitors and antibodies that target gp41...
  37. ncbi Sifuvirtide screens rigid membrane surfaces. establishment of a correlation between efficacy and membrane domain selectivity among HIV fusion inhibitor peptides
    Henri G Franquelim
    Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, 1649 028 Lisboa, Portugal
    J Am Chem Soc 130:6215-23. 2008
    ....
  38. pmc The M-T hook structure is critical for design of HIV-1 fusion inhibitors
    Huihui Chong
    MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 9 Dong Dan San Tiao, Beijing 100730, China
    J Biol Chem 287:34558-68. 2012
    ..Therefore, this study provides convincing data for our proposed concept that the M-T hook structure is critical for designing HIV-1 fusion inhibitors...
  39. ncbi Synthesized peptide inhibitors of HIV-1 gp41-dependent membrane fusion
    Yuxian He
    Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Beijing 100730, P R China
    Curr Pharm Des 19:1800-9. 2013
    ..This review highlights the development of the representative peptide inhibitors of HIV-1 fusion toward providing some insights into the future of this class of anti-HIV drugs...
  40. ncbi Resistance to enfuvirtide, the first HIV fusion inhibitor
    Michael L Greenberg
    Trimeris Inc, 4727 University Drive, Durham, NC 27707, USA
    J Antimicrob Chemother 54:333-40. 2004
    ..Reversion to a wild-type, drug-sensitive state has been reported following enfuvirtide withdrawal...
  41. ncbi New antiretroviral drugs
    R M Gulick
    Cornell HIV Clinical Trials Unit, Division of International Medicine and Infectious Diseases, Weill Medical College of Cornell University, New York, New York 10024, USA
    Clin Microbiol Infect 9:186-93. 2003
    ..Investigational HIV integrase inhibitors include S-1360. Continued progress in the treatment of HIV disease will result from the development of new antiretroviral drugs...
  42. pmc SC29EK, a peptide fusion inhibitor with enhanced alpha-helicity, inhibits replication of human immunodeficiency virus type 1 mutants resistant to enfuvirtide
    Takeshi Naito
    Laboratory of Virus Control, Institute for Virus Research, Kyoto University, Shogoin, Kyoto, Japan
    Antimicrob Agents Chemother 53:1013-8. 2009
    ..Our results show that the alpha-helicity in a peptide-based fusion inhibitor is a key factor for activity and enables the design of short peptide inhibitors with improved pharmacological properties...
  43. ncbi Molecular dynamics simulations of T-20 HIV fusion inhibitor interacting with model membranes
    A M T Martins do Canto
    Departamento de Quimica, Universidade de Evora, Portugal
    Biophys Chem 159:275-86. 2011
    ..This lower ability to interact with membranes is probably correlated with its smaller inhibitory efficiency...
  44. ncbi Sifuvirtide, a potent HIV fusion inhibitor peptide
    Rui Rui Wang
    Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
    Biochem Biophys Res Commun 382:540-4. 2009
    ..The results showed that there was cross-resistance between SFT and ENF. In conclusion, SFT is an ideal anti-HIV agent with high potency and low cytotoxicity, but may exhibit a certain extent of cross-resistance with ENF...
  45. ncbi Rapid and automated fluorescence-linked immunosorbent assay for high-throughput screening of HIV-1 fusion inhibitors targeting gp41
    Shuwen Liu
    Lindsley F Kimball Research Institute, New York Blood Center, New York, NY 10021, USA
    J Biomol Screen 8:685-93. 2003
    ..Using an Integrated Robotic Sample Processing System, this assay has been applied for high-throughput screening of organic compounds on a large scale for HIV-1 fusion inhibitors targeting gp41...
  46. ncbi Inhibiting HIV-1 entry with fusion inhibitors
    C E Baldwin
    Department of Human Retrovirology, Academic Medical Center, University of Amsterdam, The Netherlands
    Curr Med Chem 10:1633-42. 2003
    ..We will also discuss ongoing research on fusion inhibitor susceptibility testing and the development of new improved fusion inhibitors...
  47. ncbi Determination of the HIV-1 gp41 fusogenic core conformation modeled by synthetic peptides: applicable for identification of HIV-1 fusion inhibitors
    Shuwen Liu
    Lindsley F Kimball Research Institute, New York Blood Center, New York, NY 10021, USA
    Peptides 24:1303-13. 2003
    ..It suggests that these biophysical techniques can be used in a novel way to study the conformational change of gp41 during virus entry into cells and to identify HIV-1 fusion inhibitors...
  48. pmc In vivo patterns of resistance to the HIV attachment inhibitor BMS-488043
    Nannan Zhou
    Virology, Bristol Myers Squibb, Wallingford, CT 06492, USA
    Antimicrob Agents Chemother 55:729-37. 2011
    ..Most importantly, the substitutions described here are not associated with resistance to other approved antiretrovirals, and therefore, attachment inhibitors could complement the current arsenal of anti-HIV agents...
  49. ncbi Electrostatically constrained alpha-helical peptide inhibits replication of HIV-1 resistant to enfuvirtide
    Hiroki Nishikawa
    Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo ku, Kyoto 606 8501, Japan
    Int J Biochem Cell Biol 41:891-9. 2009
    ..Our approach to enhancing alpha-helicity of the peptide inhibitor may enable future design of highly effective and specific HIV-1 inhibitors...
  50. pmc Human immunodeficiency virus type 1 variants resistant to first- and second-version fusion inhibitors and cytopathic in ex vivo human lymphoid tissue
    Raghavan Chinnadurai
    Institute for Virology, University Clinic, Albert Einstein Allee 11, 89081 Ulm, Germany
    J Virol 81:6563-72. 2007
    ..Taken together, our results show that the GIV motif also plays a key role in resistance to second-version fusion inhibitors and suggest that some resistant HIV-1 variants may be pathogenic in vivo...
  51. ncbi Compensatory mutations rescue the virus replicative capacity of VIRIP-resistant HIV-1
    Emmanuel González-Ortega
    IrsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autonoma de Barcelona, Badalona, Spain
    Antiviral Res 92:479-83. 2011
    ..Our results provide additional support to the development of a new class of antiretroviral agents targeting gp41-dependent fusion...
  52. pmc Genotype and phenotype patterns of human immunodeficiency virus type 1 resistance to enfuvirtide during long-term treatment
    Stefano Menzo
    Istituto di Microbiologia e Scienze Biomediche, Universita Politecnica delle Marche, Ancona, Italy
    Antimicrob Agents Chemother 48:3253-9. 2004
    ....
  53. pmc Detailed mechanistic insights into HIV-1 sensitivity to three generations of fusion inhibitors
    Dirk Eggink
    Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam, Academic Medical Center of the University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
    J Biol Chem 284:26941-50. 2009
    ..Implications for the design of novel antiviral peptide inhibitors are discussed...
  54. pmc Identification of a critical motif for the human immunodeficiency virus type 1 (HIV-1) gp41 core structure: implications for designing novel anti-HIV fusion inhibitors
    Yuxian He
    AIDS Research Center, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
    J Virol 82:6349-58. 2008
    ..Therefore, our works provide important information for understanding the core structure of the fusion-active gp41 and for designing novel anti-HIV peptides...
  55. pmc Reduced maximal inhibition in phenotypic susceptibility assays indicates that viral strains resistant to the CCR5 antagonist maraviroc utilize inhibitor-bound receptor for entry
    Mike Westby
    Globel Research and Development, Pfizer Ltd, Sandwich Labs, Ramsgate Road, Sandwich, Kent CT13 9NJ, United Kingdom
    J Virol 81:2359-71. 2007
    ..This hypothesis was further corroborated by the observation that a high concentration of maraviroc blocks the activity of aplaviroc against maraviroc-resistant virus...
  56. ncbi Peptide and non-peptide HIV fusion inhibitors
    Shibo Jiang
    Lindsley F Kimball Research Institute, The New York Blood Center, 310 East 67th Street, New York, NY 10021, USA
    Curr Pharm Des 8:563-80. 2002
    ..in the fusion of viral and target cell membranes and serves as an attractive target for development of HIV fusion inhibitors. The extracellular domain of gp41 contains three important functional regions, i.e...
  57. pmc Potent HIV fusion inhibitors against Enfuvirtide-resistant HIV-1 strains
    Yuxian He
    Lindsley F Kimball Research Institute, New York Blood Center, New York, NY 10065, USA
    Proc Natl Acad Sci U S A 105:16332-7. 2008
    ..These findings suggest that CP32M can be further developed as an antiviral therapeutic against multidrug resistant HIV-1...
  58. pmc Putative role of membranes in the HIV fusion inhibitor enfuvirtide mode of action at the molecular level
    Salomé Veiga
    Centro de Quimica e Bioquimica, Faculdade de Ciencias da Universidade de Lisboa, Campo Grande C8, 1749 016 Lisboa, Portugal
    Biochem J 377:107-10. 2004
    ..No conformational energetic barrier prevents enfuvirtide from being active in both aqueous solution and lipidic membranes. Lipidic membranes may play a key role in the enfuvirtide biochemical mode of action...
  59. ncbi Protein design of a bacterially expressed HIV-1 gp41 fusion inhibitor
    Yiqun Deng
    Department of Biochemistry, Weill Medical College of Cornell University, New York, New York 10021, USA
    Biochemistry 46:4360-9. 2007
    ..Hence the C52L fusion inhibitor may find a practical application, for example as a vaginal or rectal microbicide to prevent HIV-1 infection in the developing world...
  60. pmc Virus-cell and cell-cell fusion mediated by the HIV-1 envelope glycoprotein is inhibited by short gp41 N-terminal membrane-anchored peptides lacking the critical pocket domain
    Yael Wexler-Cohen
    Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel
    FASEB J 24:4196-202. 2010
    ....
  61. ncbi Peptide-based inhibitors of the HIV envelope protein and other class I viral fusion proteins
    Imke Steffen
    Institute of Virology, OE 5230, Hannover Medical School, Carl Neuberg Str 1, 30625 Hannover, Germany
    Curr Pharm Des 16:1143-58. 2010
    ..Here, we will discuss how HIV mediates fusion with host cell membranes and how this process can be blocked by peptides targeting gp41. In addition, we will discuss peptide inhibitors of other class I viral fusion proteins...
  62. pmc Mutations of Gln64 in the HIV-1 gp41 N-terminal heptad repeat render viruses resistant to peptide HIV fusion inhibitors targeting the gp41 pocket
    Xiaowen Yu
    School of Life Sciences, Tsinghua University, Key Laboratory for Protein Sciences of MOE, Beijing 100084, China
    J Virol 86:589-93. 2012
    ..This report provides insights into the mechanisms of drug resistance, with implications for the design of novel HIV fusion and entry inhibitors...
  63. ncbi Subgroup analyses of maraviroc in previously treated R5 HIV-1 infection
    Gerd Fatkenheuer
    Universitätsklinik Köln, Cologne, Germany
    N Engl J Med 359:1442-55. 2008
    ....
  64. ncbi Characterization of determinants of genotypic and phenotypic resistance to enfuvirtide in baseline and on-treatment HIV-1 isolates
    Prakash R Sista
    Trimeris Inc Durham, North Carolina, Roche Biosciences, Palo Alto, California, USA
    AIDS 18:1787-94. 2004
    ..Viruses with mutations at positions 36-38 in HIV-1 gp41 and/or reduced susceptibility to ENF have been selected both in vitro and in vivo...
  65. pmc Combinations of the first and next generations of human immunodeficiency virus (HIV) fusion inhibitors exhibit a highly potent synergistic effect against enfuvirtide- sensitive and -resistant HIV type 1 strains
    Chungen Pan
    Peking University, Beijing, China
    J Virol 83:7862-72. 2009
    ..Therefore, T1249 and T1144 are being developed as the second- and third-generation HIV fusion inhibitors, respectively, with improved efficacy and drug resistance profiles...
  66. pmc Detection of low-frequency pretherapy chemokine (CXC motif) receptor 4 (CXCR4)-using HIV-1 with ultra-deep pyrosequencing
    John Archer
    University of Manchester, UK
    AIDS 23:1209-18. 2009
    ....
  67. ncbi Enfuvirtide, a new fusion inhibitor for therapy of human immunodeficiency virus infection
    Helene Hardy
    Center for HIV AIDS Care and Research, Boston Medical Center, Massachusetts 02118, USA
    Pharmacotherapy 24:198-211. 2004
    ..Given the complexity of its production and administration, however, it is likely to be most useful in antiretroviral-experienced patients...
  68. ncbi Inhibiting sexual transmission of HIV-1 infection
    Robin J Shattock
    Department of Cellular and Molecular Medicine, Infectious Diseases, St George s Hospital Medical School, London, UK
    Nat Rev Microbiol 1:25-34. 2003
    ....
  69. pmc Impact of the HIV-1 env genetic context outside HR1-HR2 on resistance to the fusion inhibitor enfuvirtide and viral infectivity in clinical isolates
    Franky Baatz
    Laboratory of Retrovirology, CRP Sante, Luxembourg, Luxembourg
    PLoS ONE 6:e21535. 2011
    ....
  70. pmc Resistance of human immunodeficiency virus type 1 to a third-generation fusion inhibitor requires multiple mutations in gp41 and is accompanied by a dramatic loss of gp41 function
    Dirk Eggink
    Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam CINIMA, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands
    J Virol 85:10785-97. 2011
    ..It requires the accumulation of multiple mutations in gp41, is accompanied with a dramatic loss of gp41 function, and induces compensatory mutations in gp120...
  71. ncbi Full fusion competence rescue of the enfuvirtide resistant HIV-1 gp41 genotype (43D) by a prevalent polymorphism (137K)
    Martin Tolstrup
    Department of Infectious Diseases, Skejby Sygehus, Aarhus University Hospital, Aarhus, Denmark
    AIDS 21:519-21. 2007
  72. ncbi Development of peptide and small-molecule HIV-1 fusion inhibitors that target gp41
    Lifeng Cai
    Department of Medicinal Chemistry, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Haidian District, Beijing 100850, China
    ChemMedChem 5:1813-24. 2010
    ..However, more work needs to be done to perfect the development of peptide and small-molecule HIV fusion inhibitors, particularly those that target gp41...
  73. pmc HIV type 1 from a patient with baseline resistance to CCR5 antagonists uses drug-bound receptor for entry
    John C Tilton
    Department of Microbiology, University of Pennsylvania, Philadelphia, 19104, USA
    AIDS Res Hum Retroviruses 26:13-24. 2010
    ..In addition, some patients can harbor CCR5 antagonist-resistant viruses prior to treatment, which may have implications for the clinical use of this new class of antiretrovirals...
  74. pmc Identification of a gp41 core-binding molecule with homologous sequence of human TNNI3K-like protein as a novel human immunodeficiency virus type 1 entry inhibitor
    Yun Zhu
    Laboratory of Immunology, School of Life Sciences, Tsinghua University, Beijing, People s Republic of China
    J Virol 84:9359-68. 2010
    ..Therefore, this peptide can be used as a lead for developing novel HIV fusion inhibitors and as a probe for studying the membrane-fusogenic mechanism of HIV.
  75. ncbi Treatment of HIV infection with the CCR5 antagonist maraviroc
    Wiete Kromdijk
    Slotervaart Hospital, Department of Pharmacy and Pharmacology, Louwesweg 6, 1066 EC Amsterdam, The Netherlands
    Expert Opin Pharmacother 11:1215-23. 2010
    ..New drug classes are thus required. Maraviroc is the first chemokine receptor 5 antagonist approved for use in treatment experienced HIV patients with a R5-tropic virus...
  76. pmc A novel chimeric protein-based HIV-1 fusion inhibitor targeting gp41 glycoprotein with high potency and stability
    Chungen Pan
    Lindsley F Kimball Research Institute, New York Blood Center, New York, New York 10065, USA
    J Biol Chem 286:28425-34. 2011
    ..coli make this novel protein-based fusion inhibitor a promising candidate for further development as an anti-HIV-1 microbicide or therapeutic for the prevention and treatment of HIV-1 infection...
  77. ncbi Design, synthesis, and biological activity of novel 5-((arylfuran/1H-pyrrol-2-yl)methylene)-2-thioxo-3-(3-(trifluoromethyl)phenyl)thiazolidin-4-ones as HIV-1 fusion inhibitors targeting gp41
    Shibo Jiang
    Lindsley F Kimball Research Institute, New York Blood Center, New York 10065, United States
    J Med Chem 54:572-9. 2011
    ..By contrast, molecular docking of 12i, a less active compound containing a pyrrole instead of a furan ring, indicated a completely different orientation from 12b and 12m and missed critical interactions...
  78. pmc Grifonin-1: a small HIV-1 entry inhibitor derived from the algal lectin, Griffithsin
    Ewa D Micewicz
    Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, United States of America
    PLoS ONE 5:e14360. 2010
    ..We used the sequence of a portion of griffithsin's sequence as a design template to create smaller peptides with antiviral and carbohydrate-binding properties...
  79. pmc Variants of human immunodeficiency virus type 1 that efficiently use CCR5 lacking the tyrosine-sulfated amino terminus have adaptive mutations in gp120, including loss of a functional N-glycan
    Emily J Platt
    Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, OR 97239 3098, USA
    J Virol 79:4357-68. 2005
    ..These results demonstrate a novel functional role for a gp120 N-linked oligosaccharide and a high degree of adaptability in coreceptor usage by HIV-1...
  80. pmc Design, synthesis, and biological evaluation of N-carboxyphenylpyrrole derivatives as potent HIV fusion inhibitors targeting gp41
    Kun Liu
    Beijing Institute of Pharmacology and Toxicology, 27 Tai Ping Road, Beijing, 100850, China
    J Med Chem 51:7843-54. 2008
    ....
  81. pmc Development of indole compounds as small molecule fusion inhibitors targeting HIV-1 glycoprotein-41
    Guangyan Zhou
    Department of Basic Sciences, Touro University California, 1310 Club Drive, Mare Island, Vallejo, California 94592, United States
    J Med Chem 54:7220-31. 2011
    ..The results enhance our understanding of indole compounds as inhibitors of gp41...
  82. pmc A small molecule HIV-1 inhibitor that targets the HIV-1 envelope and inhibits CD4 receptor binding
    Pin fang Lin
    Department of Virology, Bristol Myers Squibb, Wallingford, CT 06492, USA
    Proc Natl Acad Sci U S A 100:11013-8. 2003
    ..Together, the data show that BMS-378806 is a representative of a new class of HIV inhibitors that has the potential to become a valued addition to our current armamentarium of antiretroviral drugs...
  83. pmc Selection with a peptide fusion inhibitor corresponding to the first heptad repeat of HIV-1 gp41 identifies two genetic pathways conferring cross-resistance to peptide fusion inhibitors corresponding to the first and second heptad repeats (HR1 and HR2) of
    Wei Wang
    Center for Biologics Evaluation and Research, U S Food and Drug Administration, HFM 466, Bldg 29, Room 532, 29 Lincoln Dr, Bethesda, MD 20892, USA
    J Virol 85:12929-38. 2011
    ..The gp120 mutations alone enhanced fusion but did not appear to directly contribute to resistance. The implications of these findings for resistance mechanisms and regulation of envelope-mediated fusion are discussed...
  84. pmc A novel fluorescence intensity screening assay identifies new low-molecular-weight inhibitors of the gp41 coiled-coil domain of human immunodeficiency virus type 1
    Lifeng Cai
    Department of Basic Sciences, Touro University California, Vallejo, California 94592, USA
    Antimicrob Agents Chemother 51:2388-95. 2007
    ..In vitro syncytium inhibition assays confirmed that the compounds inhibited cell-cell fusion in the low micromolar range. These lead compounds provide a new molecular scaffold for the development of fusion inhibitors...
  85. ncbi HIV-1 gp41 fusion intermediate: a target for HIV therapeutics
    Chungen Pan
    Laboratory of Viral Immunology, Lindsley F Kimball Research Institute, New York Blood Center, New York, NY 10065, USA
    J Formos Med Assoc 109:94-105. 2010
    ..Here, we present an overview of the current development of anti-HIV drugs, particularly those targeting the gp41 fusion intermediate...
  86. ncbi Antiviral activity and safety of aplaviroc with lamivudine/zidovudine in HIV-infected, therapy-naive patients: the ASCENT (CCR102881) study
    Judith Currier
    UCLA Center for Care, Los Angeles, CA, United States
    Antivir Ther 13:297-306. 2008
    ..This Phase IIb study explored the antiviral activity and safety of the investigational CCR5 antagonist aplaviroc (APL) in antiretroviral-naive patients harbouring R5-tropic virus...
  87. ncbi Maraviroc
    Hind Fadel
    Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA
    Drugs Today (Barc) 43:749-58. 2007
    ..In these studies, maraviroc also demonstrated acceptable safety and tolerability profiles with adverse events and discontinuation rates in general comparable to those noted in the placebo arms...
  88. pmc Structure-based design, synthesis and biological evaluation of new N-carboxyphenylpyrrole derivatives as HIV fusion inhibitors targeting gp41
    Yong Wang
    State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Biomedicine and Health, The Chinese Academy of Sciences, Guangzhou 510663, China
    Bioorg Med Chem Lett 20:189-92. 2010
    ..The synthesized ligands showed significant inhibitory activities against HIV gp41 6-helix bundle formation, HIV-1 mediated cell-cell fusion and HIV-1 replication...
  89. ncbi Identification of minimal sequence for HIV-1 fusion inhibitors
    Hiroki Nishikawa
    Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo ku, Kyoto 606 8501, Japan
    Bioorg Med Chem 16:9184-7. 2008
    ....
  90. ncbi Enfuvirtide (T-20) cross-reactive glycoprotein 41 antibody does not impair the efficacy or safety of enfuvirtide
    Sharon Walmsley
    University of Toronto, Toronto, Ontario, Canada
    J Infect Dis 188:1827-33. 2003
    ..Safety was unaffected by the presence of positive antibody at any time point or change in level of antibody. There was no evidence that enfuvirtide cross-reactive gp41 antibody affects the efficacy or safety of enfuvirtide...
  91. pmc Discovery of HIV fusion inhibitors targeting gp41 using a comprehensive α-helix mimetic library
    Landon R Whitby
    Department of Chemistry, Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, United States
    Bioorg Med Chem Lett 22:2861-5. 2012
    ..6-1.3 μM) that not only match or exceed the potency of those disclosed over the past decade, but that also exhibit effective activity in a cell-cell fusion assay (IC(50) 5-8 μM)...
  92. ncbi An anti-HIV microbicide engineered in commensal bacteria: secretion of HIV-1 fusion inhibitors by lactobacilli
    Oliver Pusch
    Center of Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria
    AIDS 20:1917-22. 2006
    ..To engineer Lactobacillus spp. to secrete HIV-1 fusion inhibitors with potent neutralizing activity against primary HIV-1 isolates...
  93. pmc Trimeric, coiled-coil extension on peptide fusion inhibitor of HIV-1 influences selection of resistance pathways
    Min Zhuang
    Center for Biologics Evaluation and Research, United States Food and Drug Administration, Bethesda, Maryland 20892, USA
    J Biol Chem 287:8297-309. 2012
    ..These findings inform inhibitor design and identify regions of plasticity in the highly conserved gp41 that modulate virus entry and escape from HR1 peptide inhibitors...
  94. pmc Structural basis of potent and broad HIV-1 fusion inhibitor CP32M
    Xue Yao
    MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 9 Dong Dan San Tiao, Beijing 100730, China
    J Biol Chem 287:26618-29. 2012
    ..Therefore, our data present important information for developing novel HIV-1 fusion inhibitors for clinical use...
  95. ncbi Development of resistance to VIR-353 with cross-resistance to the natural HIV-1 entry virus inhibitory peptide (VIRIP)
    Emmanuel Gonzalez
    IrsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autonoma de Barcelona, Spain
    AIDS 25:1557-83. 2011
    ..A VIRIP analogue (VIR-576) has been shown to be effective in a phase I/II clinical trial. We have evaluated the activity and mechanism of HIV-1 resistance to VIRIP and its analogue, VIR-353...
  96. pmc Preclinical evaluation of the HIV-1 fusion inhibitor L'644 as a potential candidate microbicide
    Sarah Harman
    Centre for Infection, Division of Cellular and Molecular Medicine, St George s University of London, London, United Kingdom
    Antimicrob Agents Chemother 56:2347-56. 2012
    ..These data support the further development of L'644 for microbicide application...
  97. ncbi The role of blood cell membrane lipids on the mode of action of HIV-1 fusion inhibitor sifuvirtide
    Pedro M Matos
    Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisbon, Av Prof Egas Moniz, 1649 028 Lisboa, Portugal
    Biochem Biophys Res Commun 403:270-4. 2010
    ....
  98. ncbi A new recombinant virus system for the study of HIV-1 entry and inhibition
    Francois Roman
    Retrovirology Laboratory, Centre de Recherche Public CRP Santé, 84 rue Val Fleuri, L 1526 Luxembourg, Luxembourg
    J Virol Methods 131:99-104. 2006
    ..The system was tested showing that an isoleucine to valine substitution at residue position 37 of the HIV-1 gp41 impairs the fitness of the virus but does not lead by itself to T-20 resistance...
  99. ncbi Evolution of genotypic and phenotypic resistance during chronic treatment with the fusion inhibitor T-1249
    T Melby
    Trimeris, Inc, Morrisville, North Carolina 07560, USA
    AIDS Res Hum Retroviruses 23:1366-73. 2007
    ..These data also point toward a substantial genetic barrier and fitness cost to development of resistance to next-generation fusion inhibitors...
  100. ncbi Stopping HIV fusion with enfuvirtide: the first step to extracellular HAART
    Graeme Moyle
    HIV Research Department, Chelsea and Westminster Hospital, London, UK
    J Antimicrob Chemother 51:213-7. 2003
  101. ncbi Week-12 response to therapy as a predictor of week 24, 48, and 96 outcome in patients receiving the HIV fusion inhibitor enfuvirtide in the T-20 versus Optimized Regimen Only (TORO) trials
    Francois Raffi
    University Hospital, Nantes, France
    Clin Infect Dis 42:870-7. 2006
    ....

Research Grants62

  1. CSF Molecular Marker Study Consortium
    Richard Price; Fiscal Year: 2006
    ..abstract_text> ..
  2. Structure-based discovery and development of HIV-1 gp41 fusion inhibitors
    Miriam Gochin; Fiscal Year: 2013
    ..This proposal seeks to apply structure-aided drug design to develop low molecular weight HIV fusion inhibitors which prevent viral entry and the cell-to-cell spread that causes immune deficiency...
  3. Rational design of indole compounds as HIV fusion inhibitors
    Miriam Gochin; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Development of low molecular weight HIV fusion inhibitors based on a carboxybenzyl-substituted indole scaffold is proposed...
  4. Modified Triterpines as Potent HIV Fusion Inhibitors
    Kuo Hsiung Lee; Fiscal Year: 2012
    ..The aim is to discover an optimal compound that, with the help of a pharmaceutical partner, can be developed as an anti- AIDS clinical trial candidate and, ultimately, as a new drug to treat AIDS-infected patients. ..
  5. Rational Design of HIV Fusion Inhibitors Targeting gp41
    Shibo Jiang; Fiscal Year: 2004
    ..The long-term goal is to develop novel small molecule HIV-1 fusion inhibitors as a new class of anti-HIV-1 drugs. ..
  6. Small Molecule HIV Fusion Inhibitors
    Carl Wild; Fiscal Year: 2004
    ..2) Utilizing secondary and tertiary assays to characterize hits from the primary screen. 3) Carrying out hit-to-lead optimization using results from 4) ADME and additional virology studies. ..
  7. HIV Fusion Inhibitors
    James Tam; Fiscal Year: 2004
    ..abstract_text> ..
  8. Rational Design of HIV Fusion Inhibitors Targeting gp41
    Shibo Jiang; Fiscal Year: 2010
    ..Therefore, this research is relevant to public health. ..
  9. SARS-CoV S Protein Receptor-binding Domain-based Vaccines
    Shibo Jiang; Fiscal Year: 2010
    ..The long-term goal of this project is to develop highly effective and safe subunit vaccines for protecting at-risk populations from SARS-CoV infection or bioterrorism attack. ..
  10. Anti-HIV-1 Composite Cellulose Acetate Phthalate Film
    Shibo Jiang; Fiscal Year: 2008
    ....
  11. 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. ..
  12. ADULT AIDS CLINICAL TRIALS GROUP
    Michael Saag; Fiscal Year: 2007
    ..abstract_text> ..
  13. Modified Envelope Glycoproteins for HIV-1 Vaccine
    John P Moore; Fiscal Year: 2010
    ..11/07) Page 2 Form Page 2 ..
  14. Recombinant CCR5 Inhibitors for Topical Microbicides
    Donald Mosier; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  15. Anal Dysplasia in HIV+ and HIV- men
    Timothy Wilkin; Fiscal Year: 2006
    ..This study will help provide important new information on which groups of HIV+ men may benefit from screening and how HAART may modify this risk. ..
  16. UAB AIEDRP: Immune Control and Escape in Acute Infection
    JOHN KILBY; Fiscal Year: 2006
    ..Finally, our proposal involves collaborations with other AIEDRP units where an important exchange of patient specimens, scientific expertise, technology, and data will continue. ..
  17. Mitochondria And Metabolic Complications Of HIV
    Pablo Tebas; Fiscal Year: 2006
    ..In order to do this we will use a NASBA based assay to measure the mitochondrial DNA and RNA content in PBMCs, and use 2000 specimens collected longitudinally in 3 large ACTG studies. ..
  18. AIDS CLINICAL TRIALS UNIT
    Pablo Tebas; Fiscal Year: 2007
    ..The investigators have credentials in basic and patient-oriented clinical research. ..
  19. PEPTIDE-CELL INTERACTIONS IN SACCHAROMYCES CEREVISIAE
    Fred Naider; Fiscal Year: 2007
    ..An understanding of the interaction of ligands with GPCRs and how these interactions trigger signal transduction and are regulated is necessary to facilitate the design and synthesis of drugs to treat many diseases. ..
  20. Midcareer Investigator Award /Patient-Oriented Research
    Charles Hicks; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  21. The impact of early antiretroviral therapy on HIV persistence and inflammation
    STEVEN GRANT DEEKS; Fiscal Year: 2010
    ..Our work may also provide important insights in the role of chronic inflammation in driving viral persistence, and hence may lead to the development of novel interventions. ..
  22. Cross-reactive HERV immunity to combat HIV-1 infection
    Donald E Mosier; Fiscal Year: 2010
    ..The result will be "cross-protective" immunity, as best exemplified by the eradication of smallpox by vaccination with the related cowpox virus. ..
  23. CSF & Lymphocyte Dynamics in HIV Infection
    Richard W Price; Fiscal Year: 2010
    ..Beyond its immediate implications for prevention, diagnosis and treatment of Neuro-AIDS, it bears on the understanding other immune, inflammatory and degenerative neurological diseases. ..
  24. Novel Adenovirus Vaccine Vectors for HIV/SIV
    Dan H Barouch; Fiscal Year: 2010
    ..abstract_text> ..
  25. HIV CORECEPTOR SWITCHING
    Donald E Mosier; Fiscal Year: 2010
    ..These experiments are highly relevant to the approaching use of CCR5 inhibitors in phase III clinical trials, and may well predict the probability of resistance to this class of antivirals. ..
  26. 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. ..
  27. Optimizing Foamy Virus Vectors for Gene Therapy & Vaccine Applications
    WILLAM HARDY; Fiscal Year: 2006
    ..I am seeking a KO8 grant to allow me to expand my HIV clinical research career with basic science training to enable me to undertake translational studies directed at HIV therapeutics. ..
  28. Immunologic Control of Drug-resistant HIV-1
    Steven Deeks; Fiscal Year: 2005
    ..Finally, since we will estimate the relative in vivo thresholds for HIV-mediated immunogenicity and pathogenicity, these studies may also have implications for vaccine development. ..
  29. Immune Mechanisms and HIV Disease Pathogenesis
    Michael Lederman; Fiscal Year: 2004
    ..The proposal's specific request is for support to increase participation in the Conference by female and/or minority researchers and students. ..
  30. CONFERENCE ON HIV PATHOGENESIS
    Michael Lederman; Fiscal Year: 2005
    ....
  31. NMR STUDIES OF THE HIV ENVELOPE PROTEINS
    Michael Caffrey; Fiscal Year: 2004
    ..In this proposal, a combined approach of molecular biology, biochemistry and NMR spectroscopy will be employed. ..
  32. Drug Resistance in Non-Subtype B HIV-1
    Susan Eshleman; Fiscal Year: 2005
    ..abstract_text> ..
  33. Integrated Human Research Subjects Protection Project
    Ross McKinney; Fiscal Year: 2003
    ..abstract_text> ..
  34. CHRYSTALLIZING DISULFIDE-STABILIZED HIV-1 ENV PROTEINS
    John Moore; Fiscal Year: 2004
    ..Any information accruing from the structure of a native Env trimer could facilitate the rational design of Env-based vaccines. ..
  35. 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. ..
  36. Treatment&Pathogenesis of Cerebrospinal Fluid HIV Infect
    Richard Price; Fiscal Year: 2004
    ....
  37. Rational Design of CCR5 Antagonists as Anti-HIV-1 Drugs
    Asim Debnath; Fiscal Year: 2006
    ..The long term goal is to optimize the lead compounds through chemical syntheses and structure activity relationship (SAR) analyses and select the 3-4 best compounds for further preclinical studies. ..
  38. Treatment Intensification for Drug-Resistant HIV
    Steven Deeks; Fiscal Year: 2004
    ..Funding for the pilot clinical trial has been obtained from other sources; funding is requested in this proposal only for costs associated with the measurements of immunologic response to drug-resistant HIV-1. ..
  39. HIV NEUTRALIZATION IN VITRO & IN SHIV-INFECTED MACAQUES
    John Moore; Fiscal Year: 2001
    ....
  40. PEPTIDE-CELL INTERACTIONS IN SACCHAROMYCES CEREVISAE
    Fred Naider; Fiscal Year: 2006
    ..Overall, these studies should provide fundamental information concerning the structure and function of peptide-activated GPCRs. ..
  41. Defensins in STI-mediated enhancement of HIV Infection
    Theresa Chang; Fiscal Year: 2008
    ..A longer term outcome could be the development of novel prevention strategies. [unreadable] [unreadable] [unreadable] [unreadable]..
  42. 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. ..
  43. HIV-1 entry inhibitors targeting Phe43 cavity in gp120
    Asim Debnath; Fiscal Year: 2003
    ..The long-term goal of this proposal is to optimize the lead compounds through chemical synthesis and structure activity analyses and select 3-4 best compounds for further preclinical studies as novel ianti-HIV-1 chemotherapeutic agents. ..
  44. 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. ..
  45. Biochemical and NMR Studies of Influenza HA2
    Michael Caffrey; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  46. High Throughput Screening of HIV Entry Inhibitors (RMI)
    Michael Caffrey; Fiscal Year: 2005
    ..Specific Aim 2: Extend the HIV entry assay for discrimination between small molecule inhibitors that bind to HIV envelope proteins, from small molecule inhibitors that bind to human target receptor proteins. ..
  47. HCV Treatment Cost-Effectiveness in 3 IDU Populations
    BRUCE SCHACKMAN; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  48. 2007 Case CFAR Annual Spring Conference
    Michael Lederman; Fiscal Year: 2007
    ..The Case CFAR is proactive in its efforts to ensure inclusion of minority and female researchers in[unreadable] all aspects of Conference planning and attendance. ..
  49. Topical Immune modulatory strategies to prevent HIV transmission
    Michael Lederman; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  50. Case CFAR Meeting: HIV Pathogenesis
    Michael Lederman; Fiscal Year: 2006
    ..Presentation sessions will be Cellular Restrictions Factors; Latency; Protection from HIV Infection; Immune Pathogenesis; and Vaccines. ..
  51. 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. ..
  52. RECENT ADVANCES IN AIDS AND HIV RESEARCH
    Michael Saag; Fiscal Year: 2007
    ..CME credit for attending physicians will be provided. ..
  53. Receptor Binding of Neurotropic HIV Envelopes
    JULIO MARTIN GARCIA; Fiscal Year: 2005
    ....
  54. A Community Collaboration to Increase HIV Serostatus Awareness for At Risk AA MSM
    Melanie Thompson; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  55. Development of N-Peptides for Use in HIV-1 Topical Microbicides
    Min Lu; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  56. Mechanism of HIV-1 inhibition by alpha-defensin-1
    Theresa Chang; Fiscal Year: 2005
    ..abstract_text> ..
  57. ENTRY INHIBITORS AS TOPICAL MICROBICIDES AGAINST HIV-1
    John Moore; Fiscal Year: 2004
    ..Moore, Ph.D., Fusion-Inhibitor Acquisition, Evaluation and Formulation; Administrative Core: John P. Moore, Ph.D. ..