Capivasertib restricts sars-cov-2 cellular entry: A potential clinical application for covid-19

Sun F. Mu C. Kwok H.F. Xu J. Wu Y. Liu W. Sabatier J.-M. Annweiler C. Li X. Cao Z. Xie Y.
2021 Ivyspring International Publisher

International Journal of Biological Sciences
2021 #17 Issue 9 2348 - 2355 pp.

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.

AKT inhibitor , Antiviral activity , Capivasertib , COVID-19 , SARS-CoV-2

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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, State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Taian, 271018, China
Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Avenida de Universidade, Taipa, Macao
MoE Frontiers Science Center for Precision Oncology, University of Macau, Avenida de Universidade, Taipa, Macao
Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China
Aix-Marseille University, Institute of NeuroPhysiopathology, UMR 7051, 27, Bd Jean Moulin, Marseille cedex, 13385, France
Department of Geriatric Medicine and Memory Clinic, Research Center on Autonomy and Longevity, University Hospital, Angers, France
School of Sciences and Humanities, Biology Department, and Pilot Cluster of Multidisciplinary Comprehensive Materia Medica, Biocluster within Cluster of Life Science and Engineering at C4, Nazarbayev University, Nur-Sultan, 010000, Kazakhstan

State Key Laboratory of Virology and Modern Virology Research Center
Sino German Joint Research Center for Agricultural Biology
Institute of Translational Medicine
MoE Frontiers Science Center for Precision Oncology
Hubei Province Key Laboratory of Allergy and Immunology
Aix-Marseille University
Department of Geriatric Medicine and Memory Clinic
School of Sciences and Humanities

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