Structure of Nipah virus unassembled nucleoprotein in complex with its viral chaperone

Replication of Nipah virus, which causes human encephalitis, requires delivery of viral nucleoprotein N to the viral genome by phosphoprotein chaperone, P. The crystal structure of the N 0 –P core complex now reveals how the chaperone prevents premature N assembly on RNA and identifies a potential target for antiviral drugs. Nipah virus (NiV) is a highly pathogenic emergent paramyxovirus causing deadly encephalitis in humans. Its replication requires a constant supply of unassembled nucleoprotein (N 0 ) in complex with its viral chaperone, the phosphoprotein (P). To elucidate the chaperone function of P, we reconstituted NiV the N 0 –P core complex and determined its crystal structure. The binding of the N-terminal region of P blocks the polymerization of N by interfering with subdomain exchange between N protomers and keeps N 0 in an open conformation, ready to grasp an RNA molecule. We found that a peptide derived from the N-binding region of P protects cells against viral infection and demonstrated by structure-based mutagenesis that this peptide acts by inhibiting N 0 –P formation. These results provide new insights about the assembly of N along genomic RNA and validate the N 0 –P complex as a target for drug development.