A Novel Antiviral Target Structure Involved in the RNA Binding, Dimerization, and Nuclear Export Functions of the Influenza A Virus Nucleoprotein

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Influenza A virus nucleoprotein (NP) is a highly conserved multifunctional protein that plays an essential role in infection by all subtypes of influenza A virus, making it an attractive target for new antiviral drugs. NP regulates viral polymerase activity and transport of the viral genome into/from the host cell nucleus by forming the viral ribonucleoprotein complex (vRNP). Because NP regulates replication and transcription of the viral genome in addition to its role in nuclear export (all of which are essential for the production of viral progeny), it is a promising drug target. Here, we used the antiviral compound RK424 to identify a novel pocket structure within NP. This structure encompassed three different functional domains that are involved in the above-mentioned replication steps. RK424 inhibits viral genome replication/transcription and nuclear export of NP by destabilizing the NP oligomer and inhibiting the binding of chromosome region maintenance 1 (CRM1) to NP via nuclear export signal (NES) 3, which is located in close proximity to the NP pocket. Taken together, these findings suggest that this small NP pocket is a novel antiviral target.

Vyšlo v časopise: A Novel Antiviral Target Structure Involved in the RNA Binding, Dimerization, and Nuclear Export Functions of the Influenza A Virus Nucleoprotein. PLoS Pathog 11(7): e32767. doi:10.1371/journal.ppat.1005062
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005062

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