January 2 | 2013

Flu virus nucleoprotein

Le complexe de transcription et de réplication des virus influenza, une cible pour de nouvelles molécules antivirales

Authors | Sylvie Chenavas, Alexandre Monod, Rob W.H. Ruigrok, Thibaut Crépin

Flupharm scientists publish review about drug design targeting the polymerase complex of influenza virus in French journal.

Abstract | Transcription and replication by influenza virus are carried out by protein-RNA complexes named RNPs. There are eight of these complexes, each containing one of the eight segments of viral RNA, multiple copies of the viral nucleoprotein and each complex carries a copy of the viral RNA-dependent RNA polymerase. The polymerase itself is a complex of three subunits: PB1, PB2 and PA. Through an effort by laboratories from all over the world, atomic structures have been determined of nucleoproteins of several viral strains and of protein domains of PA and PB2. For PB1, only the structures of the small interfaces with PA and PB2 have been determined. Even though a full understanding of the fundamental processes in the viral life cycle is still lacking, the structures have revealed how nucleoprotein can oligomerize and binds to RNA, how PB1 binds to PA and how the polymerase binds to capped cellular pre-messenger RNA (mRNA) and cleaves this RNA in order to make a capped primer for its own mRNAs (cap-snatching mechanism). The structures also stimulated structure-aided drug design efforts and first generation inhibitors against nucleoprotein oligomerization, binding of PB1 to PA and the cap-snatching activity have been published. Such inhibitors may be developed into new anti-influenza drugs.
Virologie. Volume 17, Numéro 1, 6-16, Janvier-Février 2013, revue