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.

Nup37, Nup88, Nup96, Nup107, Nup133 and Nup160 belong to the so-called Nup107 subcomplex [136] , while NupL1 (Nup45/Nup58), Nup54, and Nup62 belong to the Nup62 subcomplex [137] . Other components are Magoh, ALADIN, Tpr (Translocated promoter region), EJC (exon junction complex), NLP1/CG1 (Nucleoporin-Like Protein type 1), Seh1, Rae1/Gle2 and POM121 (nuclear envelope pore membrane protein type 121) [128] . When RNPs reach the nuclear membrane, nuclear importation is mediated by the binding of the nucleoprotein with the alpha importins, which then bind importin-β [129] . Simultaneously, the importins must interact with PA, PB1 and PB2 [130] , and this affects the interaction of the RNP with the same importins [131] . Specifically, subunits PB1 and PA are imported by Ran-BP5 or karyopherin beta3 (also known as importin beta3, or importin 5), whilst subunit PB2 is imported by importin alpha-3 or importin alpha-7. NPs are imported by importin alpha-1 [132] [133] [134] [135] [136] [137] [138] [139] [140] [141] . Other molecules that take part in nuclear importation are Hsp70 and Hsp90 [142] [143] [144] . In the nucleus, the importins detach from RNP. Although it is not clear, nor is the mechanism known at the molecular level, dissociation of the RNP should occur after separation from the importins. Thus, after the spreading of RNP in the nucleoplasm, transcription and replication can initiate.