{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T18:00:04Z","timestamp":1791655204055,"version":"4.3.4"},"reference-count":63,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T00:00:00Z","timestamp":1622073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"This work was supported by the Israel Institute for Biological Chemical and Environmental Sciences","award":["SB182"],"award-info":[{"award-number":["SB182"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) global pandemic. The first step of viral infection is cell attachment, which is mediated by the binding of the SARS-CoV-2 receptor binding domain (RBD), part of the virus spike protein, to human angiotensin-converting enzyme 2 (ACE2). Therefore, drug repurposing to discover RBD-ACE2 binding inhibitors may provide a rapid and safe approach for COVID-19 therapy. Here, we describe the development of an in vitro RBD-ACE2 binding assay and its application to identify inhibitors of the interaction of the SARS-CoV-2 RBD to ACE2 by the high-throughput screening of two compound libraries (LOPAC\u00ae1280 and DiscoveryProbeTM). Three compounds, heparin sodium, aurintricarboxylic acid (ATA), and ellagic acid, were found to exert an effective binding inhibition, with IC50 values ranging from 0.6 to 5.5 \u00b5g\/mL. A plaque reduction assay in Vero E6 cells infected with a SARS-CoV-2 surrogate virus confirmed the inhibition efficacy of heparin sodium and ATA. Molecular docking analysis located potential binding sites of these compounds in the RBD. In light of these findings, the screening system described herein can be applied to other drug libraries to discover potent SARS-CoV-2 inhibitors.<\/jats:p>","DOI":"10.3390\/molecules26113213","type":"journal-article","created":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T11:07:02Z","timestamp":1622113622000},"page":"3213","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Identification of SARS-CoV-2 Receptor Binding Inhibitors by In Vitro Screening of Drug Libraries"],"prefix":"10.3390","volume":"26","author":[{"given":"Alon Ben","family":"David","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Israel Institute for Biological Chemical and Environmental Sciences, Ness Ziona 7410001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eran","family":"Diamant","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Israel Institute for Biological Chemical and Environmental Sciences, Ness Ziona 7410001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eyal","family":"Dor","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Israel Institute for Biological Chemical and Environmental Sciences, Ness Ziona 7410001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ada","family":"Barnea","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Israel Institute for Biological Chemical and Environmental Sciences, Ness Ziona 7410001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niva","family":"Natan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Israel Institute for Biological Chemical and Environmental Sciences, Ness Ziona 7410001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilach","family":"Levin","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Israel Institute for Biological Chemical and Environmental Sciences, Ness Ziona 7410001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shira","family":"Chapman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Israel Institute for Biological, Chemical and Environmental Sciences, Ness Ziona 7410001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilach Cherry","family":"Mimran","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Israel Institute for Biological Chemical and Environmental Sciences, Ness Ziona 7410001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eyal","family":"Epstein","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Israel Institute for Biological Chemical and Environmental Sciences, Ness Ziona 7410001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3249-4901","authenticated-orcid":false,"given":"Ran","family":"Zichel","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Israel Institute for Biological Chemical and Environmental Sciences, Ness Ziona 7410001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amram","family":"Torgeman","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Israel Institute for Biological Chemical and Environmental Sciences, Ness Ziona 7410001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,27]]},"reference":[{"key":"ref_1","unstructured":"WHO (2021, January 08). 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