Nipah virus RNA-directed RNA polymerase (L protein) (NiV RdRp or NiV L protein)

Nipah virus RNA-directed RNA polymerase (L protein) is the catalytic enzyme complex responsible for replicating the viral genome and synthesizing viral mRNA in Nipah virus, a highly pathogenic bat-borne zoonotic RNA virus capable of human-to-human transmission. The ~250 kDa L protein assembles with a phosphoprotein (P) cofactor to form a functional polymerase complex that catalyzes both genome replication and transcription through its multiple enzymatic domains, including the RdRp domain, PRNTase domain for capping, and methyltransferase domain. Recent structural studies using cryo-electron microscopy have revealed the molecular architecture of this polymerase complex in multiple functional states, including apo enzyme and RNA-bound elongation states, providing unprecedented insight into the mechanisms of viral RNA synthesis. The polymerase is considered an attractive therapeutic target for antiviral drug development, and the detailed structural information now available is facilitating rational design of inhibitors that could disrupt L-P interactions or block the catalytic active site. Understanding the structural basis of NiV polymerase function is critical for developing effective treatments against a virus with significant pandemic potential.

Other names

RNA-dependent RNA polymerase (RdRp)Large protein (L)L-P complex (when referring to the functional polymerase complex with the phosphoprotein)

Inhibition strategies being explored include: Direct inhibition of the RdRp catalytic domain; Disruption of the L-P protein interactions, which are essential for polymerase activity; Targeting the zinc-binding sites in the PRNTase domain, which are essential for polymerase function; Targeting the NTP entry channel. Rational drug design is being facilitated by recent cryo-electron microscopy (cryo-EM) structures that reveal the polymerase architecture in both apo and RNA-bound states.