{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T03:45:43Z","timestamp":1774928743695,"version":"3.50.1"},"reference-count":74,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,28]],"date-time":"2023-01-28T00:00:00Z","timestamp":1674864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Open Access Publishing Fund of the University of T\u00fcbingen"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has forced the development of direct-acting antiviral drugs due to the coronavirus disease 2019 (COVID-19) pandemic. The main protease of SARS-CoV-2 is a crucial enzyme that breaks down polyproteins synthesized from the viral RNA, making it a validated target for the development of SARS-CoV-2 therapeutics. New chemical phenotypes are frequently discovered in natural goods. In the current study, we used a fluorogenic assay to test a variety of natural products for their ability to inhibit SARS-CoV-2 Mpro. Several compounds were discovered to inhibit Mpro at low micromolar concentrations. It was possible to crystallize robinetin together with SARS-CoV-2 Mpro, and the X-ray structure revealed covalent interaction with the protease\u2019s catalytic Cys145 site. Selected potent molecules also exhibited antiviral properties without cytotoxicity. Some of these powerful inhibitors might be utilized as lead compounds for future COVID-19 research.<\/jats:p>","DOI":"10.3390\/ph16020190","type":"journal-article","created":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T02:54:37Z","timestamp":1675047277000},"page":"190","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Discovery of Polyphenolic Natural Products as SARS-CoV-2 Mpro Inhibitors for COVID-19"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4413-8699","authenticated-orcid":false,"given":"Nadine","family":"Kr\u00fcger","sequence":"first","affiliation":[{"name":"Infection Biology Unit, German Primate Center, Leibniz Institute for Primate Research G\u00f6ttingen, Kellnerweg 4, 37077 G\u00f6ttingen, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6933-7590","authenticated-orcid":false,"given":"Thales","family":"Kronenberger","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy, Pharmaceutical\/Medicinal Chemistry and T\u00fcbingen Center for Academic Drug Discovery, Eberhard Karls University T\u00fcbingen, Auf der Morgenstelle 8, 72076 T\u00fcbingen, Germany"},{"name":"Cluster of Excellence iFIT (EXC 2180) \u201cImage-Guided & Functionally Instructed Tumor Therapies\u201d, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}]},{"given":"Hang","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0148-9405","authenticated-orcid":false,"given":"Cheila","family":"Rocha","sequence":"additional","affiliation":[{"name":"Infection Biology Unit, German Primate Center, Leibniz Institute for Primate Research G\u00f6ttingen, Kellnerweg 4, 37077 G\u00f6ttingen, Germany"},{"name":"Faculty of Biology and Psychology, Georg-August-University G\u00f6ttingen, 37073 G\u00f6ttingen, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6086-9136","authenticated-orcid":false,"given":"Stefan","family":"P\u00f6hlmann","sequence":"additional","affiliation":[{"name":"Infection Biology Unit, German Primate Center, Leibniz Institute for Primate Research G\u00f6ttingen, Kellnerweg 4, 37077 G\u00f6ttingen, Germany"},{"name":"Faculty of Biology and Psychology, Georg-August-University G\u00f6ttingen, 37073 G\u00f6ttingen, Germany"}]},{"given":"Haixia","family":"Su","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}]},{"given":"Yechun","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China"},{"name":"State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6952-1486","authenticated-orcid":false,"given":"Stefan A.","family":"Laufer","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy, Pharmaceutical\/Medicinal Chemistry and T\u00fcbingen Center for Academic Drug Discovery, Eberhard Karls University T\u00fcbingen, Auf der Morgenstelle 8, 72076 T\u00fcbingen, Germany"},{"name":"Cluster of Excellence iFIT (EXC 2180) \u201cImage-Guided & Functionally Instructed Tumor Therapies\u201d, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5575-8896","authenticated-orcid":false,"given":"Thanigaimalai","family":"Pillaiyar","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy, Pharmaceutical\/Medicinal Chemistry and T\u00fcbingen Center for Academic Drug Discovery, Eberhard Karls University T\u00fcbingen, Auf der Morgenstelle 8, 72076 T\u00fcbingen, Germany"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1002\/med.21724","article-title":"The Recent Outbreaks of Human Coronaviruses: A Medicinal Chemistry Perspective","volume":"41","author":"Pillaiyar","year":"2021","journal-title":"Med. 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