9XD6

Crimean-Congo hemorrhagic fever virus RNA polymerase in complex with the 3' vRNA

Summary for 9XD6

• Entry DOI: 10.2210/pdb9xd6/pdb
• EMDB information: 66756
• Descriptor: RNA-directed RNA polymerase L, RNA (5'-R(*GP*GP*GP*AP*UP*UP*GP*AP*UP*AP*UP*CP*UP*UP*UP*GP*AP*GP*A)-3'), ZINC ION (3 entities in total)
• Functional Keywords: rna polymerase, virus, viral protein/rna, viral protein-rna complex
• Biological source: Crimean-Congo hemorrhagic fever virus strain IbAr10200 (CCHFV); More
• Total number of polymer chains: 2
• Total formula weight: 454713.59

Authors

Xue, L.,Gui, J.,Pan, H.,Chang, T.,Xiong, X. (deposition date: 2025-10-27, release date: 2026-05-06, Last modification date: 2026-08-05)

Primary citation

Xue, L.,Gui, J.,Pan, H.,Wu, F.,Gao, S.,Kuang, W.,Chang, T.,Li, Z.,Zou, B.,Zhao, H.,Li, M.,Zhou, M.,Yuan, H.,Rong, L.,Gong, P.,He, J.,Deng, Z.,Wang, M.,Zhan, P.,Chen, X.,Xiong, X.
Structures and inhibition of the Crimean-Congo haemorrhagic fever virus polymerase.
Nature, 2026

PubMed Abstract: Crimean-Congo haemorrhagic fever virus (CCHFV) is a tick-borne virus and causes severe, often fatal, human infections. Lacking licensed vaccines or drugs, CCHFV is a World Health Organization priority pathogen requiring urgent development of medical countermeasures. The CCHFV Large (L) protein functions as the viral RNA-dependent RNA polymerase CCHFV-L, representing a promising antiviral target, and is among the largest viral polymerases in the order Bunyavirales. Here we define the cofactors required for CCHFV-L RNA synthesis in vitro, enabling capture and determination of elongating CCHFV-L-RNA complex structures. The structures show a markedly enlarged polymerase architecture, revealing that CCHFV-L RNA synthesis is accompanied by ordering of the polymerase peripheral domains. We also define how the baloxavir-derived experimental drug WXSH0208 (ref. ) and the nucleoside analogue 2'-deoxy-2'-fluorocytidine, which has nanomolar cellular potency, inhibit this polymerase through endonuclease inhibition and post-translocation chain termination, respectively. Together, these results should structurally guide rational optimization of inhibitors directed against CCHFV-L.

PubMed: 42486991
DOI: 10.1038/s41586-026-10701-6

Experimental method

ELECTRON MICROSCOPY (2.74 Å)