22TH

Cryo-EM structure of Crimean-Congo hemorrhagic fever virus RNA polymerase in complex with suramin

Summary for 22TH

• Entry DOI: 10.2210/pdb22th/pdb
• EMDB information: 68657
• Descriptor: RNA-directed RNA polymerase L, ZINC ION, MANGANESE (II) ION, ... (5 entities in total)
• Functional Keywords: polymerase, rna binding protein
• Biological source: Crimean-Congo hemorrhagic fever virus strain IbAr10200
• Total number of polymer chains: 1
• Total formula weight: 458244.09

Authors

Ma, J.,Yang, K.,Wu, H.,Liang, Z. (deposition date: 2026-01-22, release date: 2026-08-19, Last modification date: 2026-09-16)

Primary citation

Yang, K.,Wu, H.,Liu, X.,Liang, Z.,Zou, J.,Wang, Y.,Ma, J.
Cryo-EM structures of CCHFV polymerase reveal a stepwise initiation stabilization pathway and a dual-site inhibition mechanism.
Cell Rep, 45:117945-117945, 2026

PubMed Abstract: Crimean-Congo hemorrhagic fever virus (CCHFV) is a high-priority pathogen with high case-fatality rates, yet approved therapeutics remain unavailable. The CCHFV L segment encodes a ∼450-kDa RNA-dependent RNA polymerase (L protein) orchestrating viral replication, but its structural mechanisms remain elusive. Here, we present high-resolution cryo-EM structures of the CCHFV L protein in apo, 5' vRNA-bound, 5'/3' promoter-bound, and inhibitor-bound states. The catalytic core exhibits the canonical architecture of the Bunyavirales order, featuring conserved motifs and coordinated promoter recognition via a 5' vRNA "hook" and a secondary 3' vRNA-binding site. Using suramin as a probe, we identified a dual-site mechanism of polymerase inhibition. Suramin competitively occludes the 5' vRNA-binding pocket through electrostatic mimicry of the RNA backbone and concurrently traps a distal linker-fingers interface, restricting the conformational dynamics required for catalysis. Collectively, these findings provide structural insights into CCHFV polymerase regulation and inhibition.

PubMed: 42696455
DOI: 10.1016/j.celrep.2026.117945

Experimental method

ELECTRON MICROSCOPY (2.5 Å)