Structural basis of Nipah virus RNA synthesis

Area of Science:

• Virology
• Structural Biology
• Molecular Biology

Background:

• Nipah virus (NiV) is a highly pathogenic non-segmented negative-strand RNA virus (nsNSV) with pandemic potential.
• The NiV RNA-dependent RNA polymerase (RdRp) complex (L and P proteins) is crucial for viral replication and transcription, making it a key drug target.

Purpose of the Study:

• To determine the cryo-electron microscopy (cryo-EM) structures of the NiV polymerase complex.
• To elucidate the structural mechanisms of NiV RNA replication and transcription.

Main Methods:

• Cryo-electron microscopy (cryo-EM) was used to obtain structures of the NiV L-P polymerase complex.
• Structures were determined in both apo (unbound) and early elongation states, with RNA and substrate bound.

Main Results:

• The apo NiV L-P polymerase structure reveals its overall architecture, similar to other nsNSV polymerases.
• The RNA-bound structure shows how the polymerase interacts with template and product RNA during early synthesis.
• Nucleoside triphosphates binding in the active site and RNA-induced rearrangements in the RdRp core were observed.

Conclusions:

• These are the first structural snapshots of an actively elongating nsNSV L-P complex.
• The structures provide critical insights into the mechanisms of NiV genome replication and transcription.
• Findings may inform the development of antiviral therapies against NiV and related viruses.