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Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays
Published on: October 23, 2019
The tyrosine kinase inhibitor nilotinib inhibits SARS-CoV-2 in vitro
Valeria Cagno1, Gaelle Magliocco2,3, Caroline Tapparel1
1Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Abstract:
Since the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the end of 2019, no vaccine has been approved to counter this infection and the available treatments are mainly directed against the immune pathology caused by the infection. The coronavirus disease 2019 (COVID-19) is currently causing a worldwide pandemic, pointing the urgent need for effective treatment. In such emergency, drug repurposing presents the best option for a rapid antiviral response. We assess here the in vitro activity of nilotinib, imatinib and dasatinib, three Abl tyrosine kinase inhibitors, against SARS-CoV-2. Although the last two compounds do not show antiviral efficacy, we observe inhibition with nilotinib in Vero-E6 cells and Calu-3 cells with EC50s of 1.44 μM and 3.06 μM, respectively. These values are close to the mean peak concentration of nilotinib observed at steady state in serum, making this compound a potential candidate for treatment of COVID-19 in vivo.
Insights
Nilotinib, an Abl tyrosine kinase inhibitor, shows in vitro antiviral activity against SARS-CoV-2. This finding suggests nilotinib as a potential therapeutic candidate for treating coronavirus disease 2019 (COVID-19) in vivo.
Area of Science:
- Virology
- Pharmacology
- Drug Discovery
Background:
- The COVID-19 pandemic caused by SARS-CoV-2 urgently requires effective treatments.
- Current treatments primarily address immune pathology, not the virus itself.
- Drug repurposing offers a rapid strategy for antiviral response.
Purpose of the Study:
- To evaluate the in vitro antiviral activity of three Abl tyrosine kinase inhibitors: nilotinib, imatinib, and dasatinib against SARS-CoV-2.
- To identify potential drug candidates for COVID-19 treatment through drug repurposing.
Main Methods:
- In vitro assessment of nilotinib, imatinib, and dasatinib against SARS-CoV-2.
- Testing conducted in Vero-E6 and Calu-3 cell lines.
- Determination of EC50 values for compounds exhibiting antiviral activity.
Main Results:
- Nilotinib demonstrated significant in vitro antiviral efficacy against SARS-CoV-2 in both cell lines.
- EC50 values for nilotinib were 1.44 μM in Vero-E6 cells and 3.06 μM in Calu-3 cells.
- Imatinib and dasatinib did not exhibit antiviral efficacy against SARS-CoV-2.
Conclusions:
- Nilotinib shows promising in vitro antiviral activity against SARS-CoV-2.
- The observed EC50 values for nilotinib are comparable to its therapeutic serum concentrations.
- Nilotinib is a potential candidate for further investigation and in vivo treatment of COVID-19.
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