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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

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) an...

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Autores principales: Bae, Jaehoon, Kwon, Hyung-Jun, Park, Ji Sun, Jung, Jinseok, Ryu, Young Bae, Kim, Woo Sik, Lee, Ju Huck, Jeong, Jae-Ho, Lim, Jae Sung, Lee, Woo Song, Park, Su-Jin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10046907/
https://www.ncbi.nlm.nih.gov/pubmed/36975517
http://dx.doi.org/10.3390/cimb45030147
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author Bae, Jaehoon
Kwon, Hyung-Jun
Park, Ji Sun
Jung, Jinseok
Ryu, Young Bae
Kim, Woo Sik
Lee, Ju Huck
Jeong, Jae-Ho
Lim, Jae Sung
Lee, Woo Song
Park, Su-Jin
author_facet Bae, Jaehoon
Kwon, Hyung-Jun
Park, Ji Sun
Jung, Jinseok
Ryu, Young Bae
Kim, Woo Sik
Lee, Ju Huck
Jeong, Jae-Ho
Lim, Jae Sung
Lee, Woo Song
Park, Su-Jin
author_sort Bae, Jaehoon
collection PubMed
description 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.
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spelling pubmed-100469072023-03-29 Abietane Diterpenoids Isolated from Torreya nucifera Disrupt Replication of Influenza Virus by Blocking the Phosphatidylinositol-3-Kinase (PI3K)-Akt and ERK Signaling Pathway Bae, Jaehoon Kwon, Hyung-Jun Park, Ji Sun Jung, Jinseok Ryu, Young Bae Kim, Woo Sik Lee, Ju Huck Jeong, Jae-Ho Lim, Jae Sung Lee, Woo Song Park, Su-Jin Curr Issues Mol Biol Article 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. MDPI 2023-03-09 /pmc/articles/PMC10046907/ /pubmed/36975517 http://dx.doi.org/10.3390/cimb45030147 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bae, Jaehoon
Kwon, Hyung-Jun
Park, Ji Sun
Jung, Jinseok
Ryu, Young Bae
Kim, Woo Sik
Lee, Ju Huck
Jeong, Jae-Ho
Lim, Jae Sung
Lee, Woo Song
Park, Su-Jin
Abietane Diterpenoids Isolated from Torreya nucifera Disrupt Replication of Influenza Virus by Blocking the Phosphatidylinositol-3-Kinase (PI3K)-Akt and ERK Signaling Pathway
title Abietane Diterpenoids Isolated from Torreya nucifera Disrupt Replication of Influenza Virus by Blocking the Phosphatidylinositol-3-Kinase (PI3K)-Akt and ERK Signaling Pathway
title_full Abietane Diterpenoids Isolated from Torreya nucifera Disrupt Replication of Influenza Virus by Blocking the Phosphatidylinositol-3-Kinase (PI3K)-Akt and ERK Signaling Pathway
title_fullStr Abietane Diterpenoids Isolated from Torreya nucifera Disrupt Replication of Influenza Virus by Blocking the Phosphatidylinositol-3-Kinase (PI3K)-Akt and ERK Signaling Pathway
title_full_unstemmed Abietane Diterpenoids Isolated from Torreya nucifera Disrupt Replication of Influenza Virus by Blocking the Phosphatidylinositol-3-Kinase (PI3K)-Akt and ERK Signaling Pathway
title_short Abietane Diterpenoids Isolated from Torreya nucifera Disrupt Replication of Influenza Virus by Blocking the Phosphatidylinositol-3-Kinase (PI3K)-Akt and ERK Signaling Pathway
title_sort abietane diterpenoids isolated from torreya nucifera disrupt replication of influenza virus by blocking the phosphatidylinositol-3-kinase (pi3k)-akt and erk signaling pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10046907/
https://www.ncbi.nlm.nih.gov/pubmed/36975517
http://dx.doi.org/10.3390/cimb45030147
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