tetano
Editor, Senior Moderator
Virologie (Montrouge). 2013 Feb 1;17(1):6-16. doi: 10.1684/vir.2013.0475. [h=1]Transcription and replication complex of influenza virus, a new antiviral drugs target.[/h]
Chenavas S[SUP]1[/SUP], Monod A[SUP]1[/SUP], Ruigrok RWH[SUP]1[/SUP], Cr?pin T[SUP]1[/SUP].
[h=3]Author information[/h] 1 UMI3265 UJF-EMBL-CNRS, Biologie structurale des interactions entre virus et cellule h?te, 6, rue Jules-Horowitz, BP 181, 38042 Grenoble cedex 9, France.
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] RNA polymerase; influenza; nucleoprotein; replication; transcription
PMID: 31910551 DOI: 10.1684/vir.2013.0475
Chenavas S[SUP]1[/SUP], Monod A[SUP]1[/SUP], Ruigrok RWH[SUP]1[/SUP], Cr?pin T[SUP]1[/SUP].
[h=3]Author information[/h] 1 UMI3265 UJF-EMBL-CNRS, Biologie structurale des interactions entre virus et cellule h?te, 6, rue Jules-Horowitz, BP 181, 38042 Grenoble cedex 9, France.
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] RNA polymerase; influenza; nucleoprotein; replication; transcription
PMID: 31910551 DOI: 10.1684/vir.2013.0475