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

Alejandro Peralta-Garcia, View ORCID ProfileMariona Torrens-Fontanals, Tomasz Maciej Stepniewski, Judit Grau-Expósito, David Perea, Vikram Ayinampudi, Maria Waldhoer, Mirjam Zimmermann, Maria J. Buzón, Meritxell Genescà, Jana Selent
doi: https://doi.org/10.1101/2021.09.07.459123
Alejandro Peralta-Garcia
1Research Programme on Biomedical Informatics (GRIB), Hospital Del Mar Medical Research Institute (IMIM)—Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), 08003 Barcelona, Spain
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Mariona Torrens-Fontanals
1Research Programme on Biomedical Informatics (GRIB), Hospital Del Mar Medical Research Institute (IMIM)—Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), 08003 Barcelona, Spain
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  • ORCID record for Mariona Torrens-Fontanals
Tomasz Maciej Stepniewski
1Research Programme on Biomedical Informatics (GRIB), Hospital Del Mar Medical Research Institute (IMIM)—Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), 08003 Barcelona, Spain
2InterAx Biotech AG, PARK InnovAARE, 5234 Villigen, Switzerland
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Judit Grau-Expósito
3Infectious Diseases Department, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain
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David Perea
3Infectious Diseases Department, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain
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Vikram Ayinampudi
2InterAx Biotech AG, PARK InnovAARE, 5234 Villigen, Switzerland
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Maria Waldhoer
2InterAx Biotech AG, PARK InnovAARE, 5234 Villigen, Switzerland
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Mirjam Zimmermann
2InterAx Biotech AG, PARK InnovAARE, 5234 Villigen, Switzerland
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Maria J. Buzón
3Infectious Diseases Department, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain
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Meritxell Genescà
3Infectious Diseases Department, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain
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Jana Selent
1Research Programme on Biomedical Informatics (GRIB), Hospital Del Mar Medical Research Institute (IMIM)—Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), 08003 Barcelona, Spain
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  • For correspondence: jana.selent@upf.edu
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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.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted September 07, 2021.
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Entrectinib - a SARS-CoV-2 inhibitor in Human Lung Tissue (HLT) cells
Alejandro Peralta-Garcia, Mariona Torrens-Fontanals, Tomasz Maciej Stepniewski, Judit Grau-Expósito, David Perea, Vikram Ayinampudi, Maria Waldhoer, Mirjam Zimmermann, Maria J. Buzón, Meritxell Genescà, Jana Selent
bioRxiv 2021.09.07.459123; doi: https://doi.org/10.1101/2021.09.07.459123
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Entrectinib - a SARS-CoV-2 inhibitor in Human Lung Tissue (HLT) cells
Alejandro Peralta-Garcia, Mariona Torrens-Fontanals, Tomasz Maciej Stepniewski, Judit Grau-Expósito, David Perea, Vikram Ayinampudi, Maria Waldhoer, Mirjam Zimmermann, Maria J. Buzón, Meritxell Genescà, Jana Selent
bioRxiv 2021.09.07.459123; doi: https://doi.org/10.1101/2021.09.07.459123

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