9jqk

From Proteopedia

Ebola VP30 and its inhibitor

Structural highlights

9jqk is a 4 chain structure with sequence from Ebola virus - Zaire (1995). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.29Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

VP30_EBOZ5 Acts as a transcription anti-termination factor immediately after transcription initiation, but does not affect transcription elongation. This function has been found to be dependent on the formation of an RNA stem-loop at the transcription start site of the first gene. Binds to RNA (By similarity).

Publication Abstract from PubMed

The Ebola virus, a filovirus, has been responsible for significant human fatalities since its discovery. Despite extensive research, effective small-molecule drugs remain elusive due to its complex pathogenesis. Inhibition of RNA synthesis is a promising therapeutic target, and the VP30 protein plays a critical role in this process. The interaction between VP30 and the nucleoprotein (NP) is essential for viral replication. We identified ginkgolic acid as a small molecule with strong affinity for VP30, which was validated through multiple assays, including thermal shift, surface plasmon resonance, fluorescence polarization, pull-down, and co-immunoprecipitation. The antiviral efficacy of ginkgolic acid was demonstrated in the EBOV transcription- and replication-competent virus-like particle (trVLP) system. Furthermore, we resolved the crystal structure of the VP30-ginkgolic acid complex, revealing two ginkgolic acid molecules located at the VP30/NP interaction interface. This structural information provides insight into the molecular basis of ginkgolic acid's antiviral activity and suggests a novel therapeutic strategy targeting the VP30/NP interaction.

Ginkgolic acid inhibits Ebola virus transcription and replication by disrupting the interaction between nucleoprotein and VP30 protein.,Peng C, Wu F, Ma Y, Liu G, Huang Y, Tong R, Xu W Antiviral Res. 2025 Feb;234:106074. doi: 10.1016/j.antiviral.2024.106074. Epub , 2024 Dec 22. PMID:39716669^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Peng C, Wu F, Ma Y, Liu G, Huang Y, Tong R, Xu W. Ginkgolic acid inhibits Ebola virus transcription and replication by disrupting the interaction between nucleoprotein and VP30 protein. Antiviral Res. 2025 Feb;234:106074. PMID:39716669 doi:10.1016/j.antiviral.2024.106074