RT Journal Article SR Electronic T1 Targeted Drug Repurposing Against the SARS-CoV-2 E channel Identifies Blockers With in vitro Antiviral Activity JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.02.24.432490 DO 10.1101/2021.02.24.432490 A1 Prabhat Pratap Singh Tomar A1 Miriam Krugliak A1 Isaiah Tuvia Arkin YR 2021 UL http://biorxiv.org/content/early/2021/02/24/2021.02.24.432490.abstract AB 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 StatementThe 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.