E De Clercq

Summary

Affiliation: Katholieke Universiteit Leuven
Country: Belgium

Publications

  1. doi request reprint Highlights in antiviral drug research: antivirals at the horizon
    Erik De Clercq
    Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B 3000, Leuven, Belgium
    Med Res Rev 33:1215-48. 2013
  2. doi request reprint The acyclic nucleoside phosphonates (ANPs): Antonín Holý's legacy
    Erik De Clercq
    Rega Institute for Medical Research, KU Leuven, B 3000, Leuven, Belgium
    Med Res Rev 33:1278-303. 2013
  3. doi request reprint A cutting-edge view on the current state of antiviral drug development
    Erik De Clercq
    Rega Institute for Medical Research, KU Leuven, B 3000, Leuven, Belgium
    Med Res Rev 33:1249-77. 2013
  4. pmc Establishment of a novel CCR5 and CXCR4 expressing CD4+ cell line which is highly sensitive to HIV and suitable for high-throughput evaluation of CCR5 and CXCR4 antagonists
    Katrien Princen
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, B 3000 Leuven, Belgium
    Retrovirology 1:2. 2004
  5. pmc Mycophenolate mofetil inhibits the development of Coxsackie B3-virus-induced myocarditis in mice
    Elizaveta Padalko
    Laboratory of Chemotherapy, Rega Institute, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B 3000 Leuven, Belgium
    BMC Microbiol 3:25. 2003
  6. ncbi request reprint Non-nucleoside reverse transcriptase inhibitors (NNRTIs): past, present, and future
    Erik De Clercq
    Rega Institute for Medical Research, K U Leuven, B 3000 Leuven
    Chem Biodivers 1:44-64. 2004
  7. ncbi request reprint Cidofovir in the treatment of poxvirus infections
    Erik De Clercq
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B 3000, Leuven, Belgium
    Antiviral Res 55:1-13. 2002
  8. ncbi request reprint Strategies in the design of antiviral drugs
    Erik De Clercq
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, B 3000 Leuven, Belgium
    Nat Rev Drug Discov 1:13-25. 2002
  9. ncbi request reprint Interferon and its inducers--a never-ending story: "old" and "new" data in a new perspective
    Erik De Clercq
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, B 3000, Belgium
    J Infect Dis 194:S19-26. 2006
  10. ncbi request reprint Acyclic nucleoside phosphonates: a key class of antiviral drugs
    Erik De Clercq
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, B 3000 Leuven, Belgium
    Nat Rev Drug Discov 4:928-40. 2005

Collaborators

Detail Information

Publications199 found, 100 shown here

  1. doi request reprint Highlights in antiviral drug research: antivirals at the horizon
    Erik De Clercq
    Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B 3000, Leuven, Belgium
    Med Res Rev 33:1215-48. 2013
    ..e., LJ-001 and dUY11) with broad-spectrum activity against virtually all enveloped RNA and DNA viruses...
  2. doi request reprint The acyclic nucleoside phosphonates (ANPs): Antonín Holý's legacy
    Erik De Clercq
    Rega Institute for Medical Research, KU Leuven, B 3000, Leuven, Belgium
    Med Res Rev 33:1278-303. 2013
    ..Also forthcoming are several "quad" drug combinations containing either TDF or TAF. Other ANPs, based on either an alkoxy side chain or 5-azacytosine heterocycle seem highly promising and worth further pursuing. ..
  3. doi request reprint A cutting-edge view on the current state of antiviral drug development
    Erik De Clercq
    Rega Institute for Medical Research, KU Leuven, B 3000, Leuven, Belgium
    Med Res Rev 33:1249-77. 2013
    ..e., Ebola). Whereas for HIV and HCV therapy is aimed at multiple-drug combinations, for all other viruses, HSV, CMV, VZV, pox, influenza, HBV, and filoviruses, current strategies are based on the use of single compounds...
  4. pmc Establishment of a novel CCR5 and CXCR4 expressing CD4+ cell line which is highly sensitive to HIV and suitable for high-throughput evaluation of CCR5 and CXCR4 antagonists
    Katrien Princen
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, B 3000 Leuven, Belgium
    Retrovirology 1:2. 2004
    ..Here, we describe the establishment of a novel CD4+ cell line, U87.CD4.CCR5.CXCR4, stably expressing both CCR5 and CXCR4 at the cell surface...
  5. pmc Mycophenolate mofetil inhibits the development of Coxsackie B3-virus-induced myocarditis in mice
    Elizaveta Padalko
    Laboratory of Chemotherapy, Rega Institute, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B 3000 Leuven, Belgium
    BMC Microbiol 3:25. 2003
    ..We therefore studied whether MMF, which is thus endowed with a direct antiviral as well as immunosuppressive effect, may prevent CBV-induced myocarditis in a murine model...
  6. ncbi request reprint Non-nucleoside reverse transcriptase inhibitors (NNRTIs): past, present, and future
    Erik De Clercq
    Rega Institute for Medical Research, K U Leuven, B 3000 Leuven
    Chem Biodivers 1:44-64. 2004
    ..NNRTIs have acquired a definitive position, as part of a combination regimen with NRTIs and NtRTIs, in the first-line treatment of HIV-1 infections...
  7. ncbi request reprint Cidofovir in the treatment of poxvirus infections
    Erik De Clercq
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B 3000, Leuven, Belgium
    Antiviral Res 55:1-13. 2002
    ....
  8. ncbi request reprint Strategies in the design of antiviral drugs
    Erik De Clercq
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, B 3000 Leuven, Belgium
    Nat Rev Drug Discov 1:13-25. 2002
    ..Here, I describe the rationale behind current and future drug-based strategies for combating viral infections...
  9. ncbi request reprint Interferon and its inducers--a never-ending story: "old" and "new" data in a new perspective
    Erik De Clercq
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, B 3000, Belgium
    J Infect Dis 194:S19-26. 2006
  10. ncbi request reprint Acyclic nucleoside phosphonates: a key class of antiviral drugs
    Erik De Clercq
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, B 3000 Leuven, Belgium
    Nat Rev Drug Discov 4:928-40. 2005
    ....
  11. doi request reprint The next ten stories on antiviral drug discovery (part E): advents, advances, and adventures
    Erik De Clercq
    Rega Institute for Medical Research, K U Leuven, Minderbroedersstraat 10, B 3000 Leuven, Belgium
    Med Res Rev 31:118-60. 2011
    ....
  12. ncbi request reprint New anti-HIV agents and targets
    Erik De Clercq
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, B 3000 Leuven, Belgium
    Med Res Rev 22:531-65. 2002
    ..e., azapeptidic (atazanavir)) or non-peptidic scaffold (i.e., cyclic urea (mozenavir), 4-hydroxy-2-pyrone (tipranavir)). Non-peptidic PIs may be expected to inhibit HIV mutant strains that have become resistant to peptidomimetic PIs...
  13. ncbi request reprint Hamao Umezawa Memorial Award Lecture: "An Odyssey in the Viral Chemotherapy Field"
    E De Clercq
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B 3000 Leuven, Belgium
    Int J Antimicrob Agents 18:309-28. 2001
    ....
  14. ncbi request reprint Inhibition of HIV infection by CXCR4 and CCR5 chemokine receptor antagonists
    E De Clercq
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium
    Antivir Chem Chemother 12:19-31. 2001
    ....
  15. ncbi request reprint Perspectives for the treatment of hepatitis B virus infections
    E De Clercq
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium
    Int J Antimicrob Agents 12:81-95. 1999
    ....
  16. ncbi request reprint Inhibition of HIV infection by bicyclams, highly potent and specific CXCR4 antagonists
    E De Clercq
    Rega Institute for Medical Research, Department of Microbiology and Immunology, Katholieke Universiteit, Leuven, Belgium
    Mol Pharmacol 57:833-9. 2000
    ..It is the most specific and most potent CXCR4 antagonist that has been described to date...
  17. ncbi request reprint 2001 ASPET Otto Krayer Award Lecture. Molecular targets for antiviral agents
    E De Clercq
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B 3000 Leuven, Belgium
    J Pharmacol Exp Ther 297:1-10. 2001
    ..g., respiratory syncytial virus (RSV)] and hemorrhagic fever viruses (such as Ebola virus)...
  18. pmc Vaccinia virus inhibitors as a paradigm for the chemotherapy of poxvirus infections
    E De Clercq
    Division of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, K U Leuven, B 3000 Leuven, Belgium
    Clin Microbiol Rev 14:382-97. 2001
    ..Anecdotal experience points to the efficacy of cidofovir in the treatment of the poxvirus infections molluscum contagiosum and orf (ecthyma contagiosum) in immunosuppressed patients...
  19. ncbi request reprint Carbocyclic adenosine analogues as S-adenosylhomocysteine hydrolase inhibitors and antiviral agents: recent advances
    E De Clercq
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium
    Nucleosides Nucleotides 17:625-34. 1998
    ..They also interfere with the replication of human immunodeficiency virus through inhibition of the Tat transactivation process...
  20. ncbi request reprint New developments in anti-HIV chemotherapy
    E De Clercq
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium
    Farmaco 56:3-12. 2001
    ..Given the multitude of molecular targets with which anti-HIV agents can interact, one should be cautious in extrapolating from cell-free enzymatic assays to the mode of action of these agents in intact cells...
  21. ncbi request reprint Antiviral drugs: current state of the art
    E De Clercq
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B 3000, Leuven, Belgium
    J Clin Virol 22:73-89. 2001
    ....
  22. ncbi request reprint New developments in anti-HIV chemotherapy
    E De Clercq
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B 3000 Leuven, Belgium
    Curr Med Chem 8:1543-72. 2001
    ....
  23. ncbi request reprint The emerging role of fusion inhibitors in HIV infection
    E De Clercq
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium
    Drugs R D 2:321-31. 1999
    ..The proof-of-concept that fusion inhibitors should be able to suppress viral replication in vivo has been demonstrated with pentafuside. Pentafuside and AMD 3100 have now proceeded to phase II clinical trials...
  24. ncbi request reprint Discovery and development of BVDU (brivudin) as a therapeutic for the treatment of herpes zoster
    E De Clercq
    Department of Microbiology and Immunology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat B 3000 Leuven, Belgium
    Biochem Pharmacol 68:2301-15. 2004
    ....
  25. ncbi request reprint Nucleoside analogues exerting antiviral activity through a non-nucleoside mechanism
    Erik De Clercq
    Rega Institute for Medical Research, Leuven, Belgium
    Nucleosides Nucleotides Nucleic Acids 23:457-70. 2004
    ..e. bicyclic furo[2,3-d]pyrimidine as well as HEPT and TSAO derivatives) that act against either HCMV or human immunodeficiency virus (HIV) through a non-nucleoside mode of action...
  26. ncbi request reprint 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
    ....
  27. ncbi request reprint Antivirals and antiviral strategies
    Erik De Clercq
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, B 3000 Leuven, Belgium
    Nat Rev Microbiol 2:704-20. 2004
    ..Here, the virus infections for which antiviral therapy is needed and the compounds that are available, or are being developed, for the treatment of these infections are described...
  28. ncbi request reprint Therapeutic potential of nucleoside/nucleotide analogues against poxvirus infections
    Erik De Clercq
    Rega Institute for Medical Research, K U Leuven, B 3000 Leuven, Belgium
    Rev Med Virol 14:289-300. 2004
    ..e. as 1-O-hexadecyloxypropyl-cidofovir...
  29. ncbi request reprint The bicyclam AMD3100 story
    Erik De Clercq
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, B 3000 Leuven, Belgium
    Nat Rev Drug Discov 2:581-7. 2003
    ..Here, I describe the development process of AMD3100, which began about 15 years ago with the isolation of an impurity, and the basis for the clinical application of AMD3100 and its congeners...
  30. ncbi request reprint HIV-chemotherapy and -prophylaxis: new drugs, leads and approaches
    Erik De Clercq
    Rega Institute for Medical Research, K U Leuven, Minderbroedersstraat 10, B 3000 Leuven, Belgium
    Int J Biochem Cell Biol 36:1800-22. 2004
    ..Taken together, it is obvious that the approaches for the treatment of HIV infections in recent years have become both more diverse and more efficient...
  31. ncbi request reprint (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU)
    Erik De Clercq
    Department of Microbiology and Immunology, Division of Virology and Chemotherapy, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B 3000 Leuven, Belgium
    Med Res Rev 25:1-20. 2005
    ..Numerous BVDU analogues have been described that, when equipped with this particular pharmacophore, demonstrate an activity spectrum characteristic of BVDU, including selective anti-VZV activity...
  32. pmc Clinical potential of the acyclic nucleoside phosphonates cidofovir, adefovir, and tenofovir in treatment of DNA virus and retrovirus infections
    Erik De Clercq
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, B 3000 Leuven, Belgium
    Clin Microbiol Rev 16:569-96. 2003
    ....
  33. ncbi request reprint New approaches toward anti-HIV chemotherapy
    Erik De Clercq
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B 3000 Leuven, Belgium
    J Med Chem 48:1297-313. 2005
  34. ncbi request reprint Antiviral drug discovery and development: where chemistry meets with biomedicine
    Erik De Clercq
    Rega Institute for Medical Research, K U Leuven, Minderbroedersstraat 10, B 3000 Leuven, Belgium
    Antiviral Res 67:56-75. 2005
    ....
  35. ncbi request reprint Antiviral potential of a new generation of acyclic nucleoside phosphonates, the 6-[2-(phosphonomethoxy)alkoxy]-2,4-diaminopyrimidines
    Erik De Clercq
    Address correspondence to Erik De Clercq, Rega Institute for Medical Research, K U Leuven, Minderbroedersstraat 10, Leuven B 3000, Belgium
    Nucleosides Nucleotides Nucleic Acids 24:331-41. 2005
    ..The 6-[2-(phosphonomethoxy)alkoxy]-2,4-diaminopyrimidines offer substantial potential for the treatment of a broad range of retro-, hepadna-, herpes-, adeno-, and poxvirus infections...
  36. ncbi request reprint Highlights in the development of new antiviral agents
    E De Clercq
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, B 3000, Belgium
    Mini Rev Med Chem 2:163-75. 2002
    ....
  37. ncbi request reprint Highly potent and selective inhibition of varicella-zoster virus replication by bicyclic furo[2,3-d]pyrimidine nucleoside analogues
    Erik De Clercq
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, B 3000 Leuven, Belgium
    Med Res Rev 23:253-74. 2003
    ..Further development of the furo[2,3-d]pyrimidine nucleoside analogues as new therapeutic modalities for the treatment of VZV infections (i.e., varicella and herpes zoster) seems highly justified...
  38. ncbi request reprint A second target for the peptoid Tat/transactivation response element inhibitor CGP64222: inhibition of human immunodeficiency virus replication by blocking CXC-chemokine receptor 4-mediated virus entry
    D Daelemans
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium
    Mol Pharmacol 57:116-24. 2000
    ..Mechanism of action studies revealed that CGP64222 can inhibit the HIV replicative cycle, also through a selective interaction with the CXC-chemokine receptor 4 coreceptor...
  39. ncbi request reprint 6-[2-phosphonomethoxy)alkoxy]-2,4-diaminopyrimidines: a new class of acyclic pyrimidine nucleoside phosphonates with antiviral activity
    J Balzarini
    Rega Institute for Medical Research, K U Leuven, Leuven, Belgium
    Nucleosides Nucleotides Nucleic Acids 23:1321-7. 2004
    ..The HPMPO-, PMEO- and PMPO-DAPym derivatives represent a novel well-defined subclass among the acyclic nucleoside phosphonates endowed with potent and selective antiviral activity...
  40. ncbi request reprint S-adenosylhomocysteine hydrolase inhibitors interfere with the replication of human immunodeficiency virus type 1 through inhibition of the LTR transactivation
    D Daelemans
    Rega Institute for Medical Research, Katholieke Universtiteit Leuven, Belgium
    Mol Pharmacol 52:1157-63. 1997
    ..Our results suggest that AdoHcy hydrolase and the associated S-adenosylmethionine-dependent methylation mechanism play a role in the process of long terminal repeat transactivation and, hence, HIV replication...
  41. ncbi request reprint Conversion of 2',3'-dideoxyadenosine (ddA) and 2',3'-didehydro-2',3'-dideoxyadenosine (d4A) to their corresponding aryloxyphosphoramidate derivatives markedly potentiates their activity against human immunodeficiency virus and hepatitis B virus
    J Balzarini
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium
    FEBS Lett 410:324-8. 1997
    ..Both Cf 1001 and Cf 1093 were equally efficient as 3TC (lamivudine) in inhibiting HBV replication in hepatocytes, and rank among the most potent HIV and HBV inhibitors reported so far in cell culture...
  42. pmc Phosphonylmethoxyethyl purine derivatives, a new class of anti-human immunodeficiency virus agents
    R Pauwels
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium
    Antimicrob Agents Chemother 32:1025-30. 1988
    ..Unlike 2',3'-dideoxyadenosine, these compounds were not found to be degraded by deaminases derived from bovine intestine...
  43. pmc SRR-SB3, a disulfide-containing macrolide that inhibits a late stage of the replicative cycle of human immunodeficiency virus
    M Witvrouw
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium
    Antimicrob Agents Chemother 41:262-8. 1997
    ..Time-of-addition experiments indicated that SRR-SB3 acts at a late stage of the HIV-1 replicative cycle...
  44. pmc 9-[(2RS)-3-fluoro-2-phosphonylmethoxypropyl] derivatives of purines: a class of highly selective antiretroviral agents in vitro and in vivo
    J Balzarini
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium
    Proc Natl Acad Sci U S A 88:4961-5. 1991
    ..The DNA chain-terminating properties of PMEApp and (RS)-FPMPApp seem to be a prerequisite for acyclic nucleoside phosphonates to exhibit antiretrovirus (i.e., anti-HIV) activity...
  45. ncbi request reprint Antiretrovirus specificity and intracellular metabolism of 2',3' -didehydro-2',3'-dideoxythymidine (stavudine) and its 5'-monophosphate triester prodrug So324
    J Balzarini
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium
    Mol Pharmacol 50:1207-13. 1996
    ..Alanyl d4T-MP may be considered to be an intracellular depot form of d4T and/or d4T-MP, which may account for the superior antiretroviral activity of the lipophilic d4T-MP triester So324 compared with d4T...
  46. pmc Differential antiherpesvirus and antiretrovirus effects of the (S) and (R) enantiomers of acyclic nucleoside phosphonates: potent and selective in vitro and in vivo antiretrovirus activities of (R)-9-(2-phosphonomethoxypropyl)-2,6-diaminopurine
    J Balzarini
    Rega Institute of Medical Research, Katholieke Universiteit Leuven, Belgium
    Antimicrob Agents Chemother 37:332-8. 1993
    ..In addition, upon oral administration to MSV-infected mice, (R)-PMPDAP showed marked antiretroviral efficacy...
  47. pmc The novel immunosuppressive agent mycophenolate mofetil markedly potentiates the antiherpesvirus activities of acyclovir, ganciclovir, and penciclovir in vitro and in vivo
    J Neyts
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium
    Antimicrob Agents Chemother 42:216-22. 1998
    ..These observations may have clinical implications (i) for those transplant recipients who receive both MMF and either ACV, GCV, or PCV and (ii) for the treatment of ACV-resistant mucocutaneous HSV infections...
  48. ncbi request reprint Retention of marked sensitivity to (S)-4-isopropoxycarbonyl-6-methoxy-3-(methylthiomethyl)-3,4-di hydroquin oxaline-2(1H)-thione (HBY 097) by an azidothymidine (AZT)-resistant human immunodeficiency virus type 1 (HIV-1) strain subcultured in the combined
    J Balzarini
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium
    Biochem Pharmacol 55:617-25. 1998
    ..Given the exquisite potency of a concomitant combination of 3TC and HBY 097 in suppressing virus replication, this drug combination should be further pursued in clinical trials in HIV-1-infected individuals...
  49. ncbi request reprint Intracellular metabolism of the N7-substituted acyclic nucleoside analog 2-amino-7-(1,3-dihydroxy-2-propoxymethyl)purine, a potent inhibitor of herpesvirus replication
    J Neyts
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium
    Mol Pharmacol 53:157-65. 1998
    ..S2242 was found to be a substrate (K(m) = 90 microM) for purified human deoxyguanosine kinase; the latter enzyme was stimulated 3-4-fold in HCMV-infected cells...
  50. ncbi request reprint CD26-processed RANTES(3-68), but not intact RANTES, has potent anti-HIV-1 activity
    D Schols
    Laboratory of Experimental Chemotherapy, Rega Institute for Medical Research, Leuven, Belgium
    Antiviral Res 39:175-87. 1998
    ..CD4.CCR5 cells (IC50: 13 nM). These observations point to an important role of CD26-mediated processing of RANTES in inhibiting the replication of CCR5-binding HIV strains in HIV-infected persons and in preventing the development of AIDS...
  51. ncbi request reprint Mutations in the non-nucleoside binding-pocket interfere with the multi-nucleoside resistance phenotype
    K Van Laethem
    Rega Institute for Medical Research and University Hospitals, Katholieke Universiteit Leuven, Belgium
    AIDS 15:553-61. 2001
    ..CONCLUSION: Changes in the non-nucleoside binding pocket must affect the conformation of residues at the dNTP binding site, and can result in a partial phenotypic reversal of the multi-nucleoside resistance phenotype...
  52. ncbi request reprint Highly favorable antiviral activity and resistance profile of the novel thiocarboxanilide pentenyloxy ether derivatives UC-781 and UC-82 as inhibitors of human immunodeficiency virus type 1 replication
    J Balzarini
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium
    Mol Pharmacol 50:394-401. 1996
    ....
  53. ncbi request reprint Comparative cytostatic activity of different antiherpetic drugs against herpes simplex virus thymidine kinase gene-transfected tumor cells
    J Balzarini
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium
    Mol Pharmacol 45:1253-8. 1994
    ..e., resistance to hydrolysis by thymidine phosphorylase)...
  54. pmc The antiherpesvirus activity of H2G [(R)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine] is markedly enhanced by the novel immunosuppressive agent mycophenolate mofetil
    J Neyts
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium
    Antimicrob Agents Chemother 42:3285-9. 1998
    ....
  55. pmc Suppression of the breakthrough of human immunodeficiency virus type 1 (HIV-1) in cell culture by thiocarboxanilide derivatives when used individually or in combination with other HIV-1-specific inhibitors (i.e., TSAO derivatives)
    J Balzarini
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium
    Proc Natl Acad Sci U S A 92:5470-4. 1995
    ....
  56. pmc Inhibition of T-tropic HIV strains by selective antagonization of the chemokine receptor CXCR4
    D Schols
    Laboratory of Experimental Chemotherapy, Rega Institute for Medical Research, Leuven, Belgium
    J Exp Med 186:1383-8. 1997
    ..The bicyclams are, to our knowledge, the first low molecular weight anti-HIV agents shown to act as potent and selective CXCR4 antagonists...
  57. ncbi request reprint Site-directed mutagenesis of human immunodeficiency virus type 1 reverse transcriptase at amino acid position 138
    H Pelemans
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, B-3000, Belgium
    Virology 280:97-106. 2001
    ....
  58. pmc Marked in vivo antiretrovirus activity of 9-(2-phosphonylmethoxyethyl)adenine, a selective anti-human immunodeficiency virus agent
    J Balzarini
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium
    Proc Natl Acad Sci U S A 86:332-6. 1989
    ....
  59. ncbi request reprint A novel animal model for hemangiomas: inhibition of hemangioma development by the angiogenesis inhibitor TNP-470
    S Liekens
    Rega Institute for Medical Research, University Hospitals, Leuven, Belgium
    Cancer Res 59:2376-83. 1999
    ..i. The model described here may be useful for investigating (a) the angiogenic mechanism(s) underlying hemangioma progression; and (b) the effect of anti-angiogenic compounds on vascular tumor growth...
  60. pmc Antiretroviral efficacy and pharmacokinetics of oral bis(isopropyloxycarbonyloxymethyl)-9-(2-phosphonylmethoxypropyl)adenine in mice
    L Naesens
    Rega Institute for Medical Research, Leuven, Belgium
    Antimicrob Agents Chemother 42:1568-73. 1998
    ....
  61. ncbi request reprint Potentiating effect of ribavirin on the anti-retrovirus activity of 3'-azido-2,6-diaminopurine-2',3'-dideoxyriboside in vitro and in vivo
    J Balzarini
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium
    Antiviral Res 11:161-71. 1989
    ..A slight increase in the in vivo toxicity of AzddDAPR was noted when combined with ribavirin...
  62. pmc Prevalence and characteristics of multinucleoside-resistant human immunodeficiency virus type 1 among European patients receiving combinations of nucleoside analogues
    K Van Vaerenbergh
    Rega Institute for Medical Research and University Hospitals, Leuven, Belgium
    Antimicrob Agents Chemother 44:2109-17. 2000
    ..MNR HIV-1 is found only among multinucleoside-experienced patients. Its prevalence is low in Europe, but it should be closely monitored since it seriously limits treatment options...
  63. ncbi request reprint Potentiating effect of ribavirin on the in vitro and in vivo antiretrovirus activities of 2',3'-dideoxyinosine and 2',3'-dideoxy-2,6-diaminopurine riboside
    J Balzarini
    Rega Institute for Medical Research, Catholic University of Leuven, Belgium
    J Acquir Immune Defic Syndr 3:1140-7. 1990
    ..These observations point to the potential role of ribavirin in potentiating the anti-HIV activity of DDI in AIDS patients...
  64. ncbi request reprint Intracellular metabolism of CycloSaligenyl 3'-azido-2', 3'-dideoxythymidine monophosphate, a prodrug of 3'-azido-2', 3'-dideoxythymidine (zidovudine)
    J Balzarini
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium
    Mol Pharmacol 56:1354-61. 1999
    ....
  65. ncbi request reprint In vitro selection of drug-resistant varicella-zoster virus (VZV) mutants (OKA strain): differences between acyclovir and penciclovir?
    G Andrei
    Rega Institute for Medical Research, K U Leuven, 3000 Leuven, Belgium
    Antiviral Res 61:181-7. 2004
    ..Our data thus indicate that ACV and PCV select in vitro for different drug-resistant VZV phenotypes; whether this is also the situation in vivo remains to be investigated...
  66. ncbi request reprint Processing by CD26/dipeptidyl-peptidase IV reduces the chemotactic and anti-HIV-1 activity of stromal-cell-derived factor-1alpha
    P Proost
    Laboratory of Molecular Immunology, Rega Institute for Medical Research, University of Leuven, Belgium
    FEBS Lett 432:73-6. 1998
    ..In contrast to CD26/DPP IV-processed RANTES(3-68), SDF-1alpha(3-68) had diminished potency to inhibit HIV-1 infection. Thus, CD26/DPP IV impairs the inflammatory and haematopoietic potency of chemokines but plays a dual role in AIDS...
  67. ncbi request reprint Comparison of the LiPA HIV-1 RT test, selective PCR and direct solid phase sequencing for the detection of HIV-1 drug resistance mutations
    J C Schmit
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium
    J Virol Methods 73:77-82. 1998
    ..Overall, there was a 73 to 100% concordance between the three methods. In this study, LiPA HIV-1 RT proved to be an accurate and reliable alternative to DNA sequencing for the detection of drug resistance mutations in patient samples...
  68. pmc RANTES and MCP-3 inhibit the replication of T-cell-tropic human immunodeficiency virus type 1 strains (SF-2, MN, and HE)
    D Schols
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium
    J Virol 71:7300-4. 1997
    ..This may have important implications for immunotherapeutic strategies designed to slow down disease progression in AIDS...
  69. ncbi request reprint Failure to quantify viral load with two of the three commercial methods in a pregnant woman harboring an HIV type 1 subtype G strain
    Z Debyser
    Department of Microbiology and Immunology, Rega Institute and University Hospitals, Katholieke Universiteit Leuven, Belgium
    AIDS Res Hum Retroviruses 14:453-9. 1998
    ..In the case of discrepant low viral loads determined by one amplification technique in patients with advanced clinical stage one should use an alternative quantification technique for confirmation...
  70. pmc Antiretroviral activity and pharmacokinetics in mice of oral bis(pivaloyloxymethyl)-9-(2-phosphonylmethoxyethyl)adenine, the bis(pivaloyloxymethyl) ester prodrug of 9-(2-phosphonylmethoxyethyl)adenine
    L Naesens
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium lieve naesens rega kuleuven ac be
    Antimicrob Agents Chemother 40:22-8. 1996
    ..Bis(POM)-PMEA appears to be an efficient oral prodrug of PMEA that deserves further clinical evaluation in human immunodeficiency virus-infected individuals...
  71. ncbi request reprint Mutation of Gln125 to Asn selectively abolishes the thymidylate kinase activity of herpes simplex virus type 1 thymidine kinase
    B Degreve
    Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium
    Mol Pharmacol 59:285-93. 2001
    ..e., 1-beta-D-arabinofuranosylthymine and (E)-5-(2-bromovinyl)-1-beta-D-arabinofuranosyluracil]...
  72. pmc Hydroxyurea potentiates the antiherpesvirus activities of purine and pyrimidine nucleoside and nucleoside phosphonate analogs
    J Neyts
    Rega Institute for Medical Research, K U Leuven, B 3000 Leuven, Belgium
    Antimicrob Agents Chemother 43:2885-92. 1999
    ..The possible clinical implications of these findings are discussed...
  73. pmc Novel ribofuranosylnucleoside lead compounds for potent and selective inhibitors of mitochondrial thymidine kinase-2
    J Balzarini
    Rega Institute for Medical Research, K U Leuven, Minderbroedersstraat 10, B 3000 Leuven, Belgium
    Biochem J 351:167-71. 2000
    ..It was concluded that the ribonucleosides 5-BV-Urd and 3'-AOD-5-MeUrd represent two new lead compounds for potent and selective inhibitors of mitochondrial TK-2...
  74. ncbi request reprint Diverging binding capacities of natural LD78beta isoforms of macrophage inflammatory protein-1alpha to the CC chemokine receptors 1, 3 and 5 affect their anti-HIV-1 activity and chemotactic potencies for neutrophils and eosinophils
    S Struyf
    Laboratory of Molecular Immunology, Rega Institute for Medical Research, University of Leuven, Leuven, Belgium
    Eur J Immunol 31:2170-8. 2001
    ..Taken together, both LD78beta isoforms are potent HIV-1 inhibitors (CCR5) and activators for neutrophils (CCR1) and eosinophils (CCR1, CCR3), affecting infection and inflammation...
  75. ncbi request reprint Investigations on the anti-HIV activity of 2',3'-dideoxyadenosine analogues with modifications in either the pentose or purine moiety. Potent and selective anti-HIV activity of 2,6-diaminopurine 2',3'-dideoxyriboside
    R Pauwels
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium
    Biochem Pharmacol 37:1317-25. 1988
    ..e. several pyrrolo[2,3-d]pyrimidine 2',3'-dideoxynucleosides, were investigated for their anti-HIV activity, but none of these derivatives proved as potent or selective as ddDAPR...
  76. ncbi request reprint Resistance of herpes simplex virus type 1 against different phosphonylmethoxyalkyl derivatives of purines and pyrimidines due to specific mutations in the viral DNA polymerase gene
    G Andrei
    Laboratory of Antiviral Chemotherapy, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B 3000 Leuven, Belgium
    J Gen Virol 81:639-48. 2000
    ..The different drug-resistant mutants varied in neurovirulent behaviour, the HPMPC(r) strains showing reduced neurovirulence compared with the wild-type...
  77. ncbi request reprint Antiviral activity of ganciclovir elaidic acid ester against herpesviruses
    G Andrei
    Rega Institute for Medical Research, Minderbroedersstraat 10, K U Leuven, B 3000, Leuven, Belgium
    Antiviral Res 45:157-67. 2000
    ..The elaidic acid ester of GCV should therefore be considered as a novel approach towards the treatment of HSV infections...
  78. ncbi request reprint The in vitro and in vivo anti-retrovirus activity, and intracellular metabolism of 3'-azido-2',3'-dideoxythymidine and 2',3'-dideoxycytidine are highly dependent on the cell species
    J Balzarini
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium
    Biochem Pharmacol 37:897-903. 1988
    ..Thus, much higher ddCTP than AzddTTP levels were achieved in human lymphoid cells, an observation that may be particularly relevant from a therapeutic viewpoint...
  79. ncbi request reprint Viral entry as the primary target for the anti-HIV activity of chicoric acid and its tetra-acetyl esters
    W Pluymers
    Rega Institute for Medical Research, K U Leuven, Leuven, Belgium
    Mol Pharmacol 58:641-8. 2000
    ..Although inhibition of HIV integrase activity by L-CA and its derivatives was confirmed in an oligonucleotide-driven assay, integrase carrying the G140S mutation was inhibited to the same extent as the wild-type integrase...
  80. ncbi request reprint Efficacy of oral 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine (PMEDAP) in the treatment of retrovirus and cytomegalovirus infections in mice
    L Naesens
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium
    J Med Virol 39:167-72. 1993
    ..Oral PMEDAP at doses of 100, 250, or 500 mg/kg resulted in plasma PMEDAP levels of 0.5-2.5 micrograms/ml, which were sustained for 3 or 6 hours after administration and may account for the high antiviral efficacy achieved...
  81. ncbi request reprint Potent, selective and cell-mediated inhibition of human herpesvirus 6 at an early stage of viral replication by the non-nucleoside compound CMV423
    Leen De Bolle
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, 3000, Leuven, Belgium
    Biochem Pharmacol 67:325-36. 2004
    ..We, therefore, conclude that CMV423 exerts its activity against HHV-6 through inhibition of a cellular process that is critical at early stages of viral replication and that may affect protein tyrosine kinase activity...
  82. ncbi request reprint Broad-spectrum antiviral and cytocidal activity of cyclopentenylcytosine, a carbocyclic nucleoside targeted at CTP synthetase
    E De Clercq
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium
    Biochem Pharmacol 41:1821-9. 1991
    ..Ce-Cyd should be further pursued, as such and in combination with OMP decarboxylase inhibitors, for its therapeutic potential in the treatment of both viral and neoplastic diseases...
  83. ncbi request reprint Anti-retrovirus activity of 9-(2-phosphonylmethoxyethyl)adenine (PMEA) in vivo increases when it is less frequently administered
    J Balzarini
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium
    Int J Cancer 46:337-40. 1990
    ..This unique property makes PMEA an attractive candidate for the treatment of retrovirus infections, including AIDS...
  84. pmc Concomitant combination therapy for HIV infection preferable over sequential therapy with 3TC and non-nucleoside reverse transcriptase inhibitors
    J Balzarini
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium
    Proc Natl Acad Sci U S A 93:13152-7. 1996
    ..In contrast with the sequential chemotherapy, concomitant combination treatment of HIV-1-infected cells with 3TC and a variety of NNRTIs resulted in a dramatic delay of virus breakthrough and resistance development...
  85. pmc Inhibition of human immunodeficiency virus replication by a dual CCR5/CXCR4 antagonist
    Katrien Princen
    Rega Institute for Medical Research, Minderbroedersstraat 10, B 3000 Leuven, Belgium
    J Virol 78:12996-3006. 2004
    ..AMD3451 is the first low-molecular-weight anti-HIV agent with selective HIV coreceptor, CCR5 and CXCR4, interaction...
  86. pmc The thiazolobenzimidazole TBZE-029 inhibits enterovirus replication by targeting a short region immediately downstream from motif C in the nonstructural protein 2C
    Armando M De Palma
    Rega Institute for Medical Research, Minderbroedersstraat 10, B 3000 Leuven, Belgium
    J Virol 82:4720-30. 2008
    ..The ATPase activity of 2C, however, remained unaltered in the presence of TBZE-029...
  87. ncbi request reprint Acyclic nucleoside phosphonates: past, present and future. Bridging chemistry to HIV, HBV, HCV, HPV, adeno-, herpes-, and poxvirus infections: the phosphonate bridge
    E De Clercq
    Rega Institute for Medical Research, K U Leuven, Minderbroedersstraat 10, B 3000 Leuven, Belgium
    Biochem Pharmacol 73:911-22. 2007
    ..e. PMPO-DAPy, PMEO-DAPy, HPMPO-DAPy) and cyclic nucleoside phosphonates (i.e. PMDTA, PMDTT, GS9148) have been accredited with an antiviral potency and selectivity similar to those of cidofovir, adefovir and/or tenofovir...
  88. ncbi request reprint (S)-1-(3-hydroxy-2-phosphonyl-methoxypropyl)cytosine in the therapy of thymidine kinase-positive and -deficient herpes simplex virus experimental keratitis
    P C Maudgal
    Eye Research Laboratory, Katholieke Universiteit Leuven, Belgium
    Invest Ophthalmol Vis Sci 32:1816-20. 1991
    ..In the treatment of keratitis caused by the HSV-1 TK- strain, 0.2% BVDU eyedrops were similar to placebo; 0.2% HPMPC eyedrops again had a brisk and significant healing effect (P less than 0.005)...
  89. ncbi request reprint Inhibition of the replication of the DNA polymerase M550V mutation variant of human hepatitis B virus by adefovir, tenofovir, L-FMAU, DAPD, penciclovir and lobucavir
    C Ying
    Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium
    J Viral Hepat 7:161-5. 2000
    ..All compounds were found to be almost equally effective at inhibiting HBV replication in HepAD38 cells (as in HepG2 2.2.15 cells), except for penciclovir, which was clearly less effective in HepAD38 cells...
  90. ncbi request reprint Efficacy of (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine for the treatment of lethal vaccinia virus infections in severe combined immune deficiency (SCID) mice
    J Neyts
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium
    J Med Virol 41:242-6. 1993
    ..HPMPC may be considered as a drug candidate for the treatment and prophylaxis of such complications...
  91. pmc Novel human immunodeficiency virus (HIV) inhibitors that have a dual mode of anti-HIV action
    Miguel Stevens
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, B 3000 Leuven, Belgium
    Antimicrob Agents Chemother 47:3109-16. 2003
    ....
  92. ncbi request reprint Pronounced in vitro and in vivo antiretroviral activity of 5-substituted 2,4-diamino-6-[2-(phosphonomethoxy)ethoxy] pyrimidines
    Jan Balzarini
    Rega Institute for Medical Research, K U Leuven, B 3000 Leuven, Belgium
    J Antimicrob Chemother 59:80-6. 2007
    ..To discover new potent and selective anti-human immunodeficiency virus (HIV) acyclic nucleoside phosphonate (ANP) drugs with in vivo antiretroviral activity...
  93. ncbi request reprint Specific recognition of the bicyclic pyrimidine nucleoside analogs, a new class of highly potent and selective inhibitors of varicella-zoster virus (VZV), by the VZV-encoded thymidine kinase
    Rebecca Sienaert
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium
    Mol Pharmacol 61:249-54. 2002
    ..Our observations may account for the unprecedented specificity of BCNAs as anti-VZV agents...
  94. ncbi request reprint Role of the human herpesvirus 6 u69-encoded kinase in the phosphorylation of ganciclovir
    Leen De Bolle
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium
    Mol Pharmacol 62:714-21. 2002
    ..Our results indicate that the limited phosphorylation of ganciclovir by pU69 may contribute to its modest antiviral activity against HHV-6 in certain cell systems...
  95. ncbi request reprint Effects of phosphonylmethoxyalkyl-purine and -pyrimidine derivatives on TK+ and TK- HSV-1 keratitis in rabbits
    P C Maudgal
    Eye Research Laboratory, Ophthalmology Clinic, Leuven, Belgium
    Antiviral Res 16:93-100. 1991
    ..005, compared with placebo eyedrops). Although PMEA eyedrops were less effective than HPMPA or HPMPC eyedrops, the effect of PMEA eyedrops was significantly (P less than 0.05) different from the effect of either BVDU or placebo eyedrops...
  96. pmc Antiretroviral activities of acyclic nucleoside phosphonates [9-(2-phosphonylmethoxyethyl)adenine, 9-(2-phosphonylmethoxyethyl)guanine, (R)-9-(2-phosphonylmethoxypropyl)adenine, and MDL 74,968] in cell cultures and murine sarcoma virus-infected newborn NM
    J Balzarini
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium
    Antimicrob Agents Chemother 41:611-6. 1997
    ..Treatment of the NMRI mice with PMEA, (R)-PMPA, and MDL 74,968 at 25 or 50 mg/kg resulted in a high percentage of long-term survivors...
  97. ncbi request reprint Enhanced anti-HIV-1 activity and altered chemotactic potency of NH2-terminally processed macrophage-derived chemokine (MDC) imply an additional MDC receptor
    S Struyf
    Laboratory of Molecular Immunology, Rega Institute for Medical Research, University of Leuven, Belgium
    J Immunol 161:2672-5. 1998
    ..These findings suggest that MDC recognizes another, yet unidentified, receptor. We conclude that minimal NH2-terminal truncation of MDC differentially affects its various immunologic functions...
  98. pmc Mouse adenovirus type 1 infection in SCID mice: an experimental model for antiviral therapy of systemic adenovirus infections
    L Lenaerts
    Rega Institute for Medical Research, Division of Virology and Chemotherapy, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B 3000 Leuven, Belgium
    Antimicrob Agents Chemother 49:4689-99. 2005
    ..These findings suggest that complete virus clearance during antiviral therapy for disseminated adenovirus infection may require an efficient adaptive immune response from the host...
  99. ncbi request reprint Differential patterns of intracellular metabolism of 2',3'-didehydro-2',3'-dideoxythymidine and 3'-azido-2',3'-dideoxythymidine, two potent anti-human immunodeficiency virus compounds
    J Balzarini
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium
    J Biol Chem 264:6127-33. 1989
    ..The 5'-triphosphates of AZT and D4T are equipotent in their inhibitory effects on the reverse transcriptases from human immunodeficiency virus and Moloney murine leukemia virus...
  100. pmc Recovery of humoral immunity is critical for successful antiviral therapy in disseminated mouse adenovirus type 1 infection
    L Lenaerts
    Department of Microbiology and Immunology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B 3000 Leuven, Belgium
    Antimicrob Agents Chemother 52:1462-71. 2008
    ....
  101. ncbi request reprint Dual infection with polyomavirus BK and acyclovir-resistant herpes simplex virus successfully treated with cidofovir in a bone marrow transplant recipient
    G Andrei
    Laboratory of Virology, Rega Institute for Medical Research, K U Leuven, Leuven, Belgium
    Transpl Infect Dis 9:126-31. 2007
    ..In addition, we describe here that this HSV-1 isolate possesses a unique phenotype and genotype...