Compounds with anti-influenza activity: present and future of strategies for the optimal treatment and management of influenza. Part I: influenza life-cycle and currently available drugs

GASPARINI, R.; AMICIZIA, D.; LAI, PL.; BRAGAZZI, NL.; PANATTO, D.

rmination, and with a loop of RNA at another termination [161] [162] [163] [164] . To progress, the infection requires a coordinated twoway flow between proteins synthesized in the cytoplasm (for instance M1 protein and NP) and the viral RNA that has been replicated in the nucleus. In this way, the RNP, which is full of vRNA, NP, M1, PA, PB1, PB2, and the non-structural proteins can reconstitute in the nucleus. The transcription factory is made up of components such as SFPQ/PSF (splicing factor proline-glutamine rich [164] , though its entire molecular anatomy is not known. As already mentioned, splicing mechanisms are crucial to increasing the dynamism and complexity of the influenza proteome. Specifically, the RED-SMU1 spliceosomal complex interacts with PB1 and PB2 and is responsible for the splicing of NS1. Other components of the spliceosomal complex are: EJC, SR (serine/arginine-rich proteins, such as SRp40, SRp55 and pre-mRNA Splicing Factor type 2 / Alternative Splicing Factor -SF2/ASF), NS1-BP and hnRNP K (heterogeneous nuclear ribonucleoproteins K) [165] [166] [167] [168] . Transcription and replication are enhanced by activation of the PI3K cascade via NS1 [76] .