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Targeted Drug Repurposing Against the SARS-CoV-2 E channel Identifies Blockers With in vitro Antiviral Activity

View ORCID ProfilePrabhat Pratap Singh Tomar, Miriam Krugliak, View ORCID ProfileIsaiah Tuvia Arkin
doi: https://doi.org/10.1101/2021.02.24.432490
Prabhat Pratap Singh Tomar
Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus Givat-Ram, Jerusalem 91904, Israel
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Miriam Krugliak
Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus Givat-Ram, Jerusalem 91904, Israel
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Isaiah Tuvia Arkin
Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus Givat-Ram, Jerusalem 91904, Israel
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  • For correspondence: arkin@huji.ac.il
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Abstract

It is difficult to overstate the impact that COVID-19 had on humankind. The pandemic’s etiological agent, SARS-CoV-2, is a member of the Coronaviridae, and as such, is an enveloped virus with ion channels in its membrane. Therefore, in an attempt to provide an option to curb the viral spread, we searched for blockers of its E protein viro-porin. Using three bacteria-based assays, we identified eight compounds that exhibited activity after screening a library of ca. 3000 approved-for-human-use drugs. Reassuringly, analysis of viral replication in tissue culture indicated that most of the compounds could reduce infectivity to varying extents. In conclusion, targeting a particular channel in the virus for drug repurposing may increase our arsenal of treatment options to combat COVID-19 virulence.

Significance Statement The goal of our study was to expand the treatment arsenal against COVID-19. To that end, we have decided to focus on drug therapy, and as a target - the E protein, an ion channel in the virus. Ion channels as a family are excellent drug targets, but viral channels have been underexploited for pharmaceutical point intervention. To hasten future regulatory requirements and focus the chemical search space, we screened a library of ca. 3000 approved-for-human-use drugs using three independent bacteria-based assays. Our results yielded eight compounds, which were subsequently tested for antiviral activity in tissue culture. Gratifyingly, most compounds were able to reduce viral replication, and as such, both validate our approach and potentially augment our anti-COVID tool kit.

Competing Interest Statement

The authors declare that they have filed a patent for second medicinal use of the compounds in question. In addition, I.T.A.\ has shares in a company that is in the process of commercializing the aforementioned compounds.

Footnotes

  • Conceptualization, I.T.A.; methodology, P.P.S.T and M.K.; formal analysis, I.T.A., P.P.S.T. and M.K.; investigation, P.P.S.T and M.K.; resources, I.T.A; writing-original draft preparation, I.T.A.; writing-review and editing, I.T.A. and P.P.S.T; visualization, I.T.A. and P.P.S.T.; supervision, I.T.A.; project administration,I.T.A.; funding acquisition, I.T.A.

  • The authors declare that they have filed a patent for second medicinal use of the compounds in question. In addition, I.T.A. has shares in a company that is in the process of commercializing the aforementioned compounds.

Copyright 
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 February 24, 2021.
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Targeted Drug Repurposing Against the SARS-CoV-2 E channel Identifies Blockers With in vitro Antiviral Activity
Prabhat Pratap Singh Tomar, Miriam Krugliak, Isaiah Tuvia Arkin
bioRxiv 2021.02.24.432490; doi: https://doi.org/10.1101/2021.02.24.432490
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Targeted Drug Repurposing Against the SARS-CoV-2 E channel Identifies Blockers With in vitro Antiviral Activity
Prabhat Pratap Singh Tomar, Miriam Krugliak, Isaiah Tuvia Arkin
bioRxiv 2021.02.24.432490; doi: https://doi.org/10.1101/2021.02.24.432490

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