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卡匹维地尔限制 SARS-CoV-2 细胞进入：COVID-19 的一种潜在临床应用。

Capivasertib restricts SARS-CoV-2 cellular entry: a potential clinical application for COVID-19.

机构信息

State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, 430072, China.

Sino German Joint Research Center for Agricultural Biology, and State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Tai'an, 271018, China.

出版信息

Int J Biol Sci. 2021 Jun 11;17(9):2348-2355. doi: 10.7150/ijbs.57810. eCollection 2021.

DOI:10.7150/ijbs.57810
PMID:34239361
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8241724/
Abstract

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has led to more than 150 million infections and about 3.1 million deaths up to date. Currently, drugs screened are urgently aiming to block the infection of SARS-CoV-2. Here, we explored the interaction networks of kinase and COVID-19 crosstalk, and identified phosphoinositide 3-kinase (PI3K)/AKT pathway as the most important kinase signal pathway involving COVID-19. Further, we found a PI3K/AKT signal pathway inhibitor capivasertib restricted the entry of SARS-CoV-2 into cells under non-cytotoxic concentrations. Lastly, the signal axis PI3K/AKT/FYVE finger-containing phosphoinositide kinase (PIKfyve)/PtdIns(3,5)P2 was revealed to play a key role during the cellular entry of viruses including SARS-CoV-2, possibly providing potential antiviral targets. Altogether, our study suggests that the PI3K/AKT kinase inhibitor drugs may be a promising anti-SARS-CoV-2 strategy for clinical application, especially for managing cancer patients with COVID-19 in the pandemic era.

摘要

新型冠状病毒病 2019（COVID-19）是由严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）感染引起的，迄今为止已导致超过 1.5 亿例感染和约 310 万人死亡。目前，筛选出的药物主要旨在阻止 SARS-CoV-2 的感染。在这里，我们探索了激酶与 COVID-19 相互作用的网络，并确定磷酸肌醇 3-激酶（PI3K）/AKT 途径是涉及 COVID-19 的最重要的激酶信号途径。此外，我们发现一种 PI3K/AKT 信号通路抑制剂卡比沙嗪在非细胞毒性浓度下限制 SARS-CoV-2 进入细胞。最后，揭示了信号轴 PI3K/AKT/FYVE 指状含磷肌醇激酶（PIKfyve）/PtdIns（3,5）P2 在包括 SARS-CoV-2 在内的病毒进入细胞过程中发挥关键作用，可能为抗病毒治疗提供潜在的靶点。总之，我们的研究表明，PI3K/AKT 激酶抑制剂药物可能是一种有前途的抗 SARS-CoV-2 策略，可用于临床应用，特别是在大流行时代管理患有 COVID-19 的癌症患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4215/8241724/374efa569ed0/ijbsv17p2348g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4215/8241724/867cbfce5d44/ijbsv17p2348g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4215/8241724/7f305844a9da/ijbsv17p2348g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4215/8241724/374efa569ed0/ijbsv17p2348g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4215/8241724/867cbfce5d44/ijbsv17p2348g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4215/8241724/322b0c01ebb1/ijbsv17p2348g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4215/8241724/b3466547113c/ijbsv17p2348g003.jpg
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