Eva Bettens
Tibotec
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Publication
Featured researches published by Eva Bettens.
Journal of Virology | 2006
Dirk Jochmans; Jerome Deval; Bart Rudolf Romanie Kesteleyn; Herwig Van Marck; Eva Bettens; Inky De Baere; Pascale Dehertogh; Tania Ivens; Marcia Van Ginderen; Bertrand Van Schoubroeck; Maryam Ehteshami; Piet Wigerinck; Matthias Götte; Kurt Hertogs
ABSTRACT We have discovered a novel class of human immunodeficiency virus (HIV) reverse transcriptase (RT) inhibitors that block the polymerization reaction in a mode distinct from those of the nucleoside or nucleotide RT inhibitors (NRTIs) and nonnucleoside RT inhibitors (NNRTIs). For this class of indolopyridone compounds, steady-state kinetics revealed competitive inhibition with respect to the nucleotide substrate. Despite substantial structural differences with classical chain terminators or natural nucleotides, these data suggest that the nucleotide binding site of HIV RT may accommodate this novel class of RT inhibitors. To test this hypothesis, we have studied the mechanism of action of the prototype compound indolopyridone-1 (INDOPY-1) using a variety of complementary biochemical tools. Time course experiments with heteropolymeric templates showed “hot spots” for inhibition following the incorporation of pyrimidines (T>C). Moreover, binding studies and site-specific footprinting experiments revealed that INDOPY-1 traps the complex in the posttranslocational state, preventing binding and incorporation of the next complementary nucleotide. The novel mode of action translates into a unique resistance profile. While INDOPY-1 susceptibility is unaffected by mutations associated with NNRTI or multidrug NRTI resistance, mutations M184V and Y115F are associated with decreased susceptibility, and mutation K65R confers hypersusceptibility to INDOPY-1. This resistance profile provides additional evidence for active site binding. In conclusion, this class of indolopyridones can occupy the nucleotide binding site of HIV RT by forming a stable ternary complex whose stability is mainly dependent on the nature of the primer 3′ end.
Journal of Virological Methods | 2005
Tania Ivens; Christel Van den Eynde; Koen Van Acker; Erik Nijs; Géry Karel Julia Dams; Eva Bettens; Asa Ohagen; Rudi Pauwels; Kurt Hertogs
Abstract The severity and global spread of the 2003 outbreak of the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) highlighted the risks to human health posed by emerging viral diseases and emphasized the need for specific therapeutic agents instead of relying on existing broadly active antiviral compounds. The development of rapid screening assays is essential for antiviral drug discovery. Thus, a screening system for anti-SARS-CoV agents was developed, which evaluated compound potency, specificity and cytotoxicity at the initial screening phase. Cell lines were engineered to constitutively express an enhanced green fluorescent protein (EGFP) and used to detect (1) antiviral potency in SARS-CoV infection tests; (2) antiviral specificity in tests using the porcine coronavirus transmissible gastroenteritis virus (TGEV); and (3) cytotoxicity in the same assays without virus challenge. The assay system involves minimal manipulation after assay set-up, facilitates automated read-out and minimizes risks associated with hazardous viruses. The suitability of this assay system in drug discovery was demonstrated by screening of 3388 small molecule compounds. The results show that these assays can be applied to high-throughput screening for identification of inhibitors selectively active against SARS-CoV.
Journal of Medicinal Chemistry | 2005
Jérôme Emile Georges Guillemont; Elisabeth Thérèse Jeanne Pasquier; Patrice Palandjian; Daniel F. J. Vernier; Sandrine Gaurrand; Paul J. Lewi; Jan Heeres; Marc René De Jonge; Lucien Maria Henricus Koymans; Frits Daeyaert; Maarten Vinkers; Eddy Arnold; Kalyan Das; Rudi Pauwels; Koen Andries; Marie-Pierre de Béthune; Eva Bettens; Kurt Hertogs; Piet Wigerinck; Philip Timmerman; Paul A. J. Janssen
European Journal of Medicinal Chemistry | 2007
Céline Isabelle Mordant; Benoit Antoine Schmitt; Elisabeth Thérèse Jeanne Pasquier; Christophe Demestre; Laurence Queguiner; C. Masungi; Anik Peeters; Liesbeth Smeulders; Eva Bettens; Kurt Hertogs; Jan Heeres; Paul J. Lewi; Jérôme Guillemont
Archive | 2003
Bart Rudolf Romanie Kesteleyn; De Vreken Wim Van; Natalie Maria Francisca Kindermans; Maxime Francis Jean-Marie Ghislain Canard; Kurt Hertogs; Eva Bettens; Vroey Veronique Corine Paul De; Dirk Jochmans
Archive | 2004
Jerôme Emile Georges Guillemont; Elisabeth Thérese Jeanne Pasquier; Jan Heeres; Kurt Hertogs; Eva Bettens; Paulus Joannes Lewi; Marc René De Jonge; Lucien Maria Henricus Koymans; Frederik Frans Desiré Daeyaert; Hendrik Maarten Vinkers; Paul Adriaan Jan Janssen
Archive | 2005
Bart Rudolf Romanie Kesteleyn; De Vreken Wim Van; Natalie Maria Francisca Kindermans; Maxime Francis Jean-Marie Ghislain Canard; Kurt Hertogs; Eva Bettens; Vroey Veronique Corine Paul De; Dirk Jochmans; Piet Tom Bert Paul Wigerinck; Jing Wang; Abdellah Tahri; Dominique Surleraux
Archive | 2005
Bart Rudolf Romanie Kesteleyn; De Vreken Wim Van; Natalie Maria Francisca Kindermans; Maxime Francis Jean-Marie Ghislain Canard; Kurt Hertogs; Eva Bettens; Vroey Veronique Corine Paul De; Dirk Jochmans; Piet Tom Bert Paul Wigerinck; Jing Wang; Abdellah Tahri; Dominique Surleraux
Archive | 2004
Eva Bettens; Frederik Frans Desiré Daeyaert; Jonge Marc René De; Jerôme Emile Georges Guillemont; Jan Heeres; Kurt Hertogs; Paul Adriaan Jan Janssen; Lucien Maria Henricus Koymans; Paulus Joannes Lewi; Elisabeth Thérese Jeanne Pasquier; Hendrik Maarten Vinkers
Archive | 2004
Eva Bettens; Frederik Frans Desire Daeyaert; Jonge Marc Rene De; Jérôme Emile Georges Guillemont; Jan Heeres; Kurt Hertogs; Paul A. J. Janssen; Lucien Maria Henricus Koymans; Paulus Joannes Lewi; Elisabeth Thérèse Jeanne Pasquier; Hendrik Maarten Vinkers