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

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.