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This review aims to identify the phytochemicals from five traditional medicinal plants (<jats:italic>Glycyrrhiza glabra<\/jats:italic>,<jats:italic>Nigella sativa<\/jats:italic>,<jats:italic>Curcuma longa<\/jats:italic>,<jats:italic>Tinospora cordifolia<\/jats:italic>and<jats:italic>Withania somnifera<\/jats:italic>) with high potential in modulating the main protease (Mpro) activity and cytokine storm in Covid\u201019 infection. The Mpro binding affinity of 13 plant phytochemicals were in the following order: Withanoside II&gt;withanoside IV&gt;withaferin A&gt;\u03b1\u2010hederin&gt;withanoside V&gt;sitoindoside IX&gt;glabridin&gt;liquiritigenin, nigellidine&gt;curcumin&gt;glycyrrhizin&gt;tinocordiside&gt;berberine. Among these phytochemicals, glycyrrhizin, withaferin A, curcumin, nigellidine and cordifolioside A suppressed SARS\u2010CoV\u20102 replication and showed stronger anti\u2010inflammatory activities than standard Covid\u201019 drugs. Both preclinical and clinical evidences supported the development of plant bioactive compounds as Mpro inhibitors.<\/jats:p>","DOI":"10.1002\/cbdv.202200655","type":"journal-article","created":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T17:09:11Z","timestamp":1663693751000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["The Efficacy of Traditional Medicinal Plants in Modulating the Main Protease of SARS\u2010CoV\u20102 and Cytokine Storm"],"prefix":"10.1002","volume":"19","author":[{"given":"Jomin","family":"Choe","sequence":"first","affiliation":[{"name":"School of Biosciences Faculty of Science and Engineering University of Nottingham Malaysia 43500 Selangor Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5888-9856","authenticated-orcid":false,"given":"Phaik","family":"Har Yong","sequence":"additional","affiliation":[{"name":"School of Bioscience Faculty of Medicine Bioscience and Nursing MAHSA University 42610 Selangor Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9423-7206","authenticated-orcid":false,"given":"Zhi","family":"Xiang Ng","sequence":"additional","affiliation":[{"name":"School of Biosciences Faculty of Science and Engineering University of Nottingham Malaysia 43500 Selangor Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,10,10]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13049-021-00846-w"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jctb.6641"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2020.05.003"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb4489"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-020-0178-y"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines9050436"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.22211.2"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2223-y"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.22207\/JPAM.14.SPL1.22"},{"key":"e_1_2_9_10_1","first-page":"1","article-title":"\u2018SARS-CoV-2 Mpro inhibitors: identification of anti-SARS-CoV-2 Mpro compounds from FDA approved drugs\u2019","author":"Bharadwaj S.","year":"2020","journal-title":"J. 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