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The Ebola virus nucleoprotein (NP) is a multifunctional structural protein essential for the life cycle of the Ebola virus (UniProt P18272). Its primary function is to encapsidate the viral negative-strand RNA genome, protecting it from host cell degradation and forming the helical nucleocapsid (PubMed: 25552713). This nucleocapsid serves as the template for viral transcription and replication, processes mediated by the interaction of NP with the viral polymerase (L) and the polymerase cofactor VP35 (PubMed: 28978444). NP is highly expressed in infected cells and is the most abundant protein in the virion, making it the primary target for rapid diagnostic tests (RDTs) and enzyme-linked immunosorbent assays (ELISA) used to detect Ebola virus disease (CDC, 2023). While current FDA-approved treatments like Inmazeb target the viral glycoprotein, NP is being actively investigated as a therapeutic target for small molecule inhibitors that aim to disrupt its assembly or its interaction with VP35 (PubMed: 30108113). Such inhibitors could potentially offer broad-spectrum activity across different ebolavirus species due to the relatively high conservation of NP compared to the glycoprotein.
Disruption of viral nucleocapsid assembly and inhibition of the viral polymerase complex by blocking NP-NP or NP-VP35 protein-protein interactions.
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