Academic Journal

In vitro Anti-Hantavirus Activity of Protein Kinase Inhibitor 8G1 Targeting AKT/mTOR/eIF4E Signaling Pathway

التفاصيل البيبلوغرافية
العنوان: In vitro Anti-Hantavirus Activity of Protein Kinase Inhibitor 8G1 Targeting AKT/mTOR/eIF4E Signaling Pathway
المؤلفون: Zhoupeng Li, Fang Wang, Qikang Ying, Dehui Kong, Xiaoxiao Zhang, Yuhang Dong, Yongsheng Liu, Dongsheng Zhai, Zhou Chen, Min Jia, Xiaoyan Xue, Mingkai Li, Xingan Wu
المصدر: Frontiers in Microbiology, Vol 13 (2022)
بيانات النشر: Frontiers Media S.A., 2022.
سنة النشر: 2022
المجموعة: LCC:Microbiology
مصطلحات موضوعية: Hantaan virus, protein kinase, inhibitor, the mammalian target of rapamycin, nucleocapsid protein, Microbiology, QR1-502
الوصف: 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.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1664-302X
Relation: https://www.frontiersin.org/articles/10.3389/fmicb.2022.880258/full; https://doaj.org/toc/1664-302X
DOI: 10.3389/fmicb.2022.880258
URL الوصول: https://doaj.org/article/93cade32278a4b7e85a8af6380dace9e
رقم الانضمام: edsdoj.93cade32278a4b7e85a8af6380dace9e
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:1664302X
DOI:10.3389/fmicb.2022.880258