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bioRxiv · 10.1101/2024.05.29.596445

Structural and functional analysis of the Nipah virus polymerase complex

Hu, S.·Kim, H.·Yang, P.·Yu, Z.·Ludeke, B.·Mobilia, S.·Pan, J.·Stratton, M.·Bian, Y.·Fearns, R.·Abraham, J.
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Abstract

Nipah virus (NiV) is a bat-borne, zoonotic RNA virus that is among the most pathogenic viruses known to humans. The NiV polymerase, which mediates viral genome replication and mRNA transcription, is a drug target. However, NiV polymerase structures were previously unavailable. We determined the cryo-EM structure of the NiV polymerase complex, comprising the large protein (L) and its associated co-factor (P), and performed structural, biophysical, and functional analyses of the NiV polymerase. The complex assembles with a long P tetrameric coiled-coil that is capped by a bundle of -helices that we show are likely dynamic in solution. Highly conserved zinc-binding modules in the capping domain and a large insert in the RdRp palm domain that is short or absent in most other non-segmented negative strand RNA viruses are critical for replication and transcription. Our findings have the potential to aid in the rational development of drugs to combat NiV infection.

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Hu, S., Kim, H., Yang, P., Yu, Z., Ludeke, B., Mobilia, S., Pan, J., Stratton, M., Bian, Y., Fearns, R., Abraham, J.. 2024-05-29. Structural and functional analysis of the Nipah virus polymerase complex. https://doi.org/10.1101/2024.05.29.596445

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