Entrectinib - a SARS-CoV-2 inhibitor in Human Lung Tissue (HLT) cells

Peralta-Garcia, A.; Torrens-Fontanals, M.; Stepniewski, T. M.; Grau-Exposito, J.; Perea, D.; Ayinampudi, V.; Waldhoer, M.; Zimmermann, M.; Buzon, M. J.; Genesca, M.; Selent, J.

doi:10.1101/2021.09.07.459123

bioRxiv · 10.1101/2021.09.07.459123

Entrectinib - a SARS-CoV-2 inhibitor in Human Lung Tissue (HLT) cells

Peralta-Garcia, A.·Torrens-Fontanals, M.·Stepniewski, T. M.·Grau-Exposito, J.·Perea, D.·Ayinampudi, V.·Waldhoer, M.·Zimmermann, M.·Buzon, M. J.·Genesca, M.·Selent, J.

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Abstract

Since the start of the COVID-19 outbreak, pharmaceutical companies and research groups have focused on the development of vaccines and antiviral drugs against SARS-CoV-2. Here, we apply a drug repurposing strategy to identify potential drug candidates that are able to block the entrance of the virus into human cells. By combining virtual screening with in vitro pseudovirus assays and antiviral assays in Human Lung Tissue (HLT) cells, we identify entrectinib as a promising antiviral drug. We found that part of the antiviral action of entrectinib is mediated by a non-specific mechanism, likely occurring at the viral membrane level. Such a profile could provide entrectinib with protection against the development of drug resistance by emerging SARS-CoV-2 variants.

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Peralta-Garcia, A., Torrens-Fontanals, M., Stepniewski, T. M., Grau-Exposito, J., Perea, D., Ayinampudi, V., Waldhoer, M., Zimmermann, M., Buzon, M. J., Genesca, M., Selent, J.. 2021-09-07. Entrectinib - a SARS-CoV-2 inhibitor in Human Lung Tissue (HLT) cells. https://doi.org/10.1101/2021.09.07.459123

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