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Ebola VP30 and its inhibitor
Structural highlights
FunctionVP30_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 PubMedThe 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
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