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

authors

• Sun Fang
• Mu Chenglin
• Kwok Hang Fai
• Xu Jiyuan
• Wu Yingliang
• Liu Wanhong
• Sabatier Jean-Marc
• Annweiler Cédric
• Li Xugang
• Cao Zhijian
• Xie Yingqiu

keywords

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

document type

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.

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