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

Area of Science:

• Virology
• Molecular Biology
• Pharmacology

Background:

• Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has resulted in millions of infections and deaths globally.
• Urgent need for effective antiviral drugs to combat the SARS-CoV-2 pandemic.
• Kinase signaling pathways are implicated in viral infections, necessitating investigation into their role in COVID-19.

Purpose of the Study:

• To explore the crosstalk between kinase signaling pathways and COVID-19.
• To identify key kinase pathways involved in SARS-CoV-2 infection.
• To evaluate potential therapeutic strategies targeting identified pathways.

Main Methods:

• Bioinformatic analysis of kinase-COVID-19 interaction networks.
• In vitro experiments using PI3K/AKT pathway inhibitors.
• Cellular assays to assess viral entry inhibition by capivasertib.
• Investigation of the PI3K/AKT/PIKfyve/PtdIns(3,5)P2 axis in viral cellular entry.

Main Results:

• The phosphoinositide 3-kinase (PI3K)/AKT pathway was identified as a critical kinase pathway in COVID-19.
• Capivasertib, a PI3K/AKT inhibitor, demonstrated efficacy in restricting SARS-CoV-2 entry into cells at non-cytotoxic concentrations.
• The PI3K/AKT/PIKfyve/PtdIns(3,5)P2 signaling axis was found to be essential for the cellular entry of SARS-CoV-2 and other viruses.

Conclusions:

• The PI3K/AKT pathway plays a significant role in SARS-CoV-2 infection.
• PI3K/AKT pathway inhibitors represent a promising therapeutic strategy against SARS-CoV-2.
• Targeting the PI3K/AKT/PIKfyve/PtdIns(3,5)P2 axis offers potential for novel antiviral treatments, particularly for cancer patients with COVID-19.