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In vitro Anti-Hantavirus Activity of Protein Kinase Inhibitor 8G1 Targeting AKT/mTOR/eIF4E Signaling Pathway
Hantaan virus (HTNV) is the main cause of hemorrhagic fever with renal syndrome (HFRS) around the world, which results in profound morbidity and mortality. However, there are currently no FDA-approved therapeutics or vaccines against HFRS. To find new anti-HTNV drugs, the inhibitory activity of 901...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279581/ https://www.ncbi.nlm.nih.gov/pubmed/35847100 http://dx.doi.org/10.3389/fmicb.2022.880258 |
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author | Li, Zhoupeng Wang, Fang Ying, Qikang Kong, Dehui Zhang, Xiaoxiao Dong, Yuhang Liu, Yongsheng Zhai, Dongsheng Chen, Zhou Jia, Min Xue, Xiaoyan Li, Mingkai Wu, Xingan |
author_facet | Li, Zhoupeng Wang, Fang Ying, Qikang Kong, Dehui Zhang, Xiaoxiao Dong, Yuhang Liu, Yongsheng Zhai, Dongsheng Chen, Zhou Jia, Min Xue, Xiaoyan Li, Mingkai Wu, Xingan |
author_sort | Li, Zhoupeng |
collection | PubMed |
description | Hantaan virus (HTNV) is the main cause of hemorrhagic fever with renal syndrome (HFRS) around the world, which results in profound morbidity and mortality. However, there are currently no FDA-approved therapeutics or vaccines against HFRS. To find new anti-HTNV drugs, the inhibitory activity of 901 small molecule kinase inhibitors against HTNV is analyzed. Among these compounds, compound 8G1 inhibits HTNV with a relatively high inhibition rate and lower toxicity. The viral titer and nucleocapsid protein of HTNV are reduced after compound 8G1 treatment in a dose-dependent manner at concentrations ranging from 1 to 20 μM. In addition, the administration of compound 8G1 at the early stage of HTNV infection can inhibit the replication of HTNV. The molecular docking result reveals that compound 8G1 forms interactions with the key amino acid residues of serine/threonine-protein kinase B (Akt), which is responsible for the observed affinity. Then, the mammalian target of rapamycin (mTOR) and eukaryotic translation initiation factor 4E (eIF4E) signaling pathways are inhibited. Our results may help to design novel targets for therapeutic intervention against HTNV infection and to understand the anti-HTNV mechanism of protein kinase inhibitors. |
format | Online Article Text |
id | pubmed-9279581 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92795812022-07-15 In vitro Anti-Hantavirus Activity of Protein Kinase Inhibitor 8G1 Targeting AKT/mTOR/eIF4E Signaling Pathway Li, Zhoupeng Wang, Fang Ying, Qikang Kong, Dehui Zhang, Xiaoxiao Dong, Yuhang Liu, Yongsheng Zhai, Dongsheng Chen, Zhou Jia, Min Xue, Xiaoyan Li, Mingkai Wu, Xingan Front Microbiol Microbiology Hantaan virus (HTNV) is the main cause of hemorrhagic fever with renal syndrome (HFRS) around the world, which results in profound morbidity and mortality. However, there are currently no FDA-approved therapeutics or vaccines against HFRS. To find new anti-HTNV drugs, the inhibitory activity of 901 small molecule kinase inhibitors against HTNV is analyzed. Among these compounds, compound 8G1 inhibits HTNV with a relatively high inhibition rate and lower toxicity. The viral titer and nucleocapsid protein of HTNV are reduced after compound 8G1 treatment in a dose-dependent manner at concentrations ranging from 1 to 20 μM. In addition, the administration of compound 8G1 at the early stage of HTNV infection can inhibit the replication of HTNV. The molecular docking result reveals that compound 8G1 forms interactions with the key amino acid residues of serine/threonine-protein kinase B (Akt), which is responsible for the observed affinity. Then, the mammalian target of rapamycin (mTOR) and eukaryotic translation initiation factor 4E (eIF4E) signaling pathways are inhibited. Our results may help to design novel targets for therapeutic intervention against HTNV infection and to understand the anti-HTNV mechanism of protein kinase inhibitors. Frontiers Media S.A. 2022-06-30 /pmc/articles/PMC9279581/ /pubmed/35847100 http://dx.doi.org/10.3389/fmicb.2022.880258 Text en Copyright © 2022 Li, Wang, Ying, Kong, Zhang, Dong, Liu, Zhai, Chen, Jia, Xue, Li and Wu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology Li, Zhoupeng Wang, Fang Ying, Qikang Kong, Dehui Zhang, Xiaoxiao Dong, Yuhang Liu, Yongsheng Zhai, Dongsheng Chen, Zhou Jia, Min Xue, Xiaoyan Li, Mingkai Wu, Xingan In vitro Anti-Hantavirus Activity of Protein Kinase Inhibitor 8G1 Targeting AKT/mTOR/eIF4E Signaling Pathway |
title | In vitro Anti-Hantavirus Activity of Protein Kinase Inhibitor 8G1 Targeting AKT/mTOR/eIF4E Signaling Pathway |
title_full | In vitro Anti-Hantavirus Activity of Protein Kinase Inhibitor 8G1 Targeting AKT/mTOR/eIF4E Signaling Pathway |
title_fullStr | In vitro Anti-Hantavirus Activity of Protein Kinase Inhibitor 8G1 Targeting AKT/mTOR/eIF4E Signaling Pathway |
title_full_unstemmed | In vitro Anti-Hantavirus Activity of Protein Kinase Inhibitor 8G1 Targeting AKT/mTOR/eIF4E Signaling Pathway |
title_short | In vitro Anti-Hantavirus Activity of Protein Kinase Inhibitor 8G1 Targeting AKT/mTOR/eIF4E Signaling Pathway |
title_sort | in vitro anti-hantavirus activity of protein kinase inhibitor 8g1 targeting akt/mtor/eif4e signaling pathway |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279581/ https://www.ncbi.nlm.nih.gov/pubmed/35847100 http://dx.doi.org/10.3389/fmicb.2022.880258 |
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