English: The targets of anti-influenza agents that are currently licensed or under clinically investigation. Before attachment of the influenza virus particle (IVP) to the host cell, specific neutralizing monoclonal antibodies (mAbs) against conserved domains in HA can prevent viral infection. Enzymatic destruction of the receptor determinant can further prevent IVP-binding to the target cells. After binding of the IVP to host cell sialic-acid receptors the viral life-cycle is continued by receptor-mediated endocytosis, HA-mediated fusion of the viral membrane with vesicular membrane, vRNP uncoating and release into the cytosol. The viral genome is then replicated/transcribed in the nucleus. After the viral mRNA has been translated into proteins some undergo post-translational processing in the cytosol or support genome replication in the nucleus. Newly formed vRNPs are exported from the nucleus and finally progeny virions are assembled and released by budding from the infected cell to infect new cells. These different processes are potential targets for the currently licensed antiviral drugs and others, which are in clinical trials including CR6261, CR8020, MEDI8852, MHAA4549A, VIS-410 (neutralizing Abs); DAS181 (sialidase); Umifenovir (fusion inhibitor); adamantanes (M2 channel blockers); Favipiravir and Ribavirin (RdRp inhibitors); VX-787 (PB2 cap-binding inhibitor); S-033188 (PA endonuclease inhibitor); AVI-7100 (inhibits M1/M2 mRNA-splicing); Nitazoxanide (HA maturation inhibitor); and Oseltamivir, Peramivir, Zanamivir, and Laninamivir (Neuraminidase inhibitors). In addition to its NF-κB inhibition effect, LASAG antagonizes the nuclear export of viral genomes and thereby blocks the assembly and release of mature influenza virus.
Date
Source
Zoonotic Potential of Influenza A Viruses: A Comprehensive Overview. In: MDPI: Viruses.
doi:10.3390/v10090497.
Author
Ahmed Mostafa, Elsayed M. Abdelwhab, Thomas C. Mettenleiter, and Stephan Pleschka
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The targets of anti-influenza agents that are currently licensed or under clinically investigation.
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