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.

The first important event during infection in humans is the attachment of influenza virions to the apical cell surface (event known also as virus adsorption). Indeed, the entry of the Influenza virus into target cells is an essential process whereby viral genomes are delivered from extracellular virions to sites of transcription/replication in the cell nucleus [54] . During this phase, thanks to the surface glycoprotein HA, the virus interacts with (-2,3)or (-2,6)-linked sialic acid receptors [55] . The physicochemical conformation of these receptors is not identical in different species of animals -humans, seals, birds, pigs, horses, etc., which are the natural reservoir of the virus. The vast majority of human receptors are located in the upper respiratory tract, but man also possesses receptors typical of birds, which are located deep in the respiratory tract [56] . 1 . Schematic representation of the replication cycle of the influenza: 1) attachment of the virion to target cells and receptor binding (virus adsorption); 2) internalization into cellular regions by means of clathrin-mediated endocytosis (Cme), caveolae-dependent endocytosis (Cde), clathrin-caveolae-independent endocytosis, and macropinocytosis; 3) endosomal trafficking via endosomes / caveosome / macropinosome / lysosomes to the perinuclear compartment; 4) ph-dependent fusion of viral and endosomal / organellar membranes; 5) uncoating; 6) nuclear importation; 7) transcription and replication; 8) nuclear exportation; 9) protein synthesis; 10) post-translational processing and trafficking; 11) viral progeny assembly and packaging; 12) budding; and 13) release. For further details, the reader is referred to the text.