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

Authors :
Zhijian Cao
Xugang Li
Wanhong Liu
Yingliang Wu
Fang Sun
Jean-Marc Sabatier
Cédric Annweiler
Yingqiu Xie
Jiyuan Xu
Chenglin Mu
Hang Fai Kwok
Institut de neurophysiopathologie (INP)
Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)
Source :
International Journal of Biological Sciences, International Journal of Biological Sciences, Ivyspring International Publisher, 2021, 17 (9), pp.2348-2355. ⟨10.7150/ijbs.57810⟩, International Journal of Biological Sciences, 2021, 17 (9), pp.2348-2355. ⟨10.7150/ijbs.57810⟩
Publication Year :
2021

Abstract

International audience; 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.

Details

ISSN :
14492288
Volume :
17
Issue :
9
Database :
OpenAIRE
Journal :
International journal of biological sciences
Accession number :
edsair.doi.dedup.....16bb76c8c1830161edf52674a936828f
Full Text :
https://doi.org/10.7150/ijbs.57810⟩