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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
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.
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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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