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Abietane Diterpenoids Isolated from Torreya nucifera Disrupt Replication of Influenza Virus by Blocking the Phosphatidylinositol-3-Kinase (PI3K)-Akt and ERK Signaling Pathway

Authors :
Jaehoon Bae
Hyung-Jun Kwon
Ji Sun Park
Jinseok Jung
Young Bae Ryu
Woo Sik Kim
Ju Huck Lee
Jae-Ho Jeong
Jae Sung Lim
Woo Song Lee
Su-Jin Park
Source :
Current Issues in Molecular Biology, Vol 45, Iss 3, Pp 2284-2295 (2023)
Publication Year :
2023
Publisher :
MDPI AG, 2023.

Abstract

Although vaccines and antiviral drugs are available, influenza viruses continue to pose a significant threat to vulnerable populations globally. With the emergence of drug-resistant strains, there is a growing need for novel antiviral therapeutic approaches. We found that 18-hydroxyferruginol (1) and 18-oxoferruginol (2) isolated from Torreya nucifera exhibited strong anti-influenza activity, with 50% inhibitory concentration values of 13.6 and 18.3 μM against H1N1, 12.8 and 10.8 μM against H9N2, and 29.2 μM (only compound 2) against H3N2 in the post-treatment assay, respectively. During the viral replication stages, the two compounds demonstrated stronger inhibition of viral RNA and protein in the late stages (12–18 h) than in the early stages (3–6 h). Moreover, both compounds inhibited PI3K-Akt signaling, which participates in viral replication during the later stages of infection. The ERK signaling pathway is also related to viral replication and was substantially inhibited by the two compounds. In particular, the inhibition of PI3K-Akt signaling by these compounds inhibited viral replication by sabotaging influenza ribonucleoprotein nucleus-to-cytoplasm export. These data indicate that compounds 1 and 2 could potentially reduce viral RNA and viral protein levels by inhibiting the PI3K-Akt signaling pathway. Our results suggest that abietane diterpenoids isolated from T. nucifera may be potent antiviral candidates for new influenza therapies.

Details

Language :
English
ISSN :
14673045 and 14673037
Volume :
45
Issue :
3
Database :
Directory of Open Access Journals
Journal :
Current Issues in Molecular Biology
Publication Type :
Academic Journal
Accession number :
edsdoj.491eebd95ed54500b79692866cd4a74f
Document Type :
article
Full Text :
https://doi.org/10.3390/cimb45030147