Annelies Stevaert

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The influenza virus PA endonuclease, which cleaves capped cellular pre-mRNAs to prime viral mRNA synthesis, is a promising target for novel anti-influenza virus therapeutics. The catalytic center of this enzyme resides in the N-terminal part of PA (PA-Nter) and contains two (or possibly one or three) Mg(2+) or Mn(2+) ions, which are critical for its(More)
The influenza virus PA endonuclease is an attractive target for development of novel anti-influenza virus therapeutics. Reported PA inhibitors chelate the divalent metal ion(s) in the enzyme's catalytic site, which is located in the N-terminal part of PA (PA-Nter). In this work, a series of 2-hydroxybenzamide-based compounds have been synthesized and(More)
The influenza virus RNA-dependent RNA polymerase complex (RdRp), a heterotrimeric protein complex responsible for viral RNA transcription and replication, represents a primary target for antiviral drug development. One particularly attractive approach is interference with the endonucleolytic "cap-snatching" reaction by the RdRp subunit PA, more precisely by(More)
The influenza virus PA endonuclease is an attractive target for the development of novel anti-influenza virus therapeutics, which are urgently needed because of the emergence of drug-resistant viral strains. Reported PA inhibitors are assumed to chelate the divalent metal ion(s) (Mg2+ or Mn2+) in the enzyme’s catalytic site, which is located in the(More)
Uridine-based nucleoside analogues have often been found to have relatively poor antiviral activity. Enzymatic assays, evaluating inhibition of influenza virus RNA polymerase, revealed that some uridine triphosphate derivatives displayed inhibitory activity on UTP incorporation into viral RNA. Here we report the synthesis, antiviral activity and enzymatic(More)
The influenza virus PA endonuclease, which cleaves capped host pre-mRNAs to initiate synthesis of viral mRNA, is a prime target for antiviral therapy. The diketo acid compound L-742,001 was previously identified as a potent inhibitor of the influenza virus endonuclease reaction, but information on its precise binding mode to PA or potential resistance(More)
Acylhydrazones are very versatile ligands and their coordination properties can be easily tuned, giving rise to metal complexes with different nuclearities. In the last few years, we have been looking for new pharmacophores able to coordinate simultaneously two metal ions, because many enzymes have two metal ions in the active site and their coordination(More)
Influenza viruses cause seasonal epidemics and pandemic outbreaks associated with significant morbidity and mortality, and a huge cost. Since resistance to the existing anti-influenza drugs is rising, innovative inhibitors with a different mode of action are urgently needed. The influenza polymerase complex is widely recognized as a key drug target, given(More)
Adequate response to severe influenza infections or pandemic outbreaks requires two complementary strategies: preventive vaccination and antiviral therapy. The existing influenza drugs, M2 blockers and neuraminidase inhibitors, show modest clinical efficacy and established or potential resistance. In the past three years, several new agents have entered the(More)
Influenza virus PA endonuclease has recently emerged as an attractive target for the development of novel antiviral therapeutics. This is an enzyme with divalent metal ion(s) (Mg(2+) or Mn(2+)) in its catalytic site: chelation of these metal cofactors is an attractive strategy to inhibit enzymatic activity. Here we report the activity of a series of(More)