{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T02:32:42Z","timestamp":1790389962822,"version":"4.1.0"},"reference-count":29,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Saudi Ministry of Health","award":["contract number 16581700012 - project number 581"],"award-info":[{"award-number":["contract number 16581700012 - project number 581"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>SARS CoV-2 pandemic is still considered a global health disaster, and newly emerged variants keep growing. A number of promising vaccines have been recently developed as a protective measure; however, cost-effective treatments are also of great importance to support this critical situation. Previously, betulinic acid has shown promising antiviral activity against SARS CoV via targeting its main protease. Herein, we investigated the inhibitory potential of this compound together with three other triterpene congeners (i.e., ursolic acid, maslinic acid, and betulin) derived from olive leaves against the viral main protease (Mpro) of the currently widespread SARS CoV-2. Interestingly, betulinic, ursolic, and maslinic acids showed significant inhibitory activity (IC50 = 3.22\u201314.55 \u00b5M), while betulin was far less active (IC50 = 89.67 \u00b5M). A comprehensive in-silico analysis (i.e., ensemble docking, molecular dynamic simulation, and binding-free energy calculation) was then performed to describe the binding mode of these compounds with the enzyme catalytic active site and determine the main essential structural features required for their inhibitory activity. Results presented in this communication indicated that this class of compounds could be considered as a promising lead scaffold for developing cost-effective anti-SARS CoV-2 therapeutics.<\/jats:p>","DOI":"10.3390\/molecules26092654","type":"journal-article","created":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T21:35:39Z","timestamp":1619904939000},"page":"2654","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Olive-Derived Triterpenes Suppress SARS COV-2 Main Protease: A Promising Scaffold for Future Therapeutics"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4822-1895","authenticated-orcid":false,"given":"Hani A.","family":"Alhadrami","sequence":"first","affiliation":[{"name":"Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, P.O. Box 80402, Jeddah 21589, Saudi Arabia"},{"name":"Special Infectious Agent Unit, King Fahd Medical Research Centre, King Abdulaziz University, P.O. Box 80402, Jeddah 21589, Saudi Arabia"},{"name":"Molecular Diagnostic Lab, King Abdulaziz University Hospital, King Abdulaziz University, P.O. Box 80402, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1442-183X","authenticated-orcid":false,"given":"Ahmed M.","family":"Sayed","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Nahda University, Beni-Suef 62513, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed M.","family":"Sharif","sequence":"additional","affiliation":[{"name":"Special Infectious Agent Unit, King Fahd Medical Research Centre, King Abdulaziz University, P.O. Box 80402, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1736-181X","authenticated-orcid":false,"given":"Esam I.","family":"Azhar","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, P.O. Box 80402, Jeddah 21589, Saudi Arabia"},{"name":"Special Infectious Agent Unit, King Fahd Medical Research Centre, King Abdulaziz University, P.O. Box 80402, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4043-2687","authenticated-orcid":false,"given":"Mostafa E.","family":"Rateb","sequence":"additional","affiliation":[{"name":"School of Computing, Engineering &amp; Physical Sciences, University of the West of Scotland, Paisley PA1 2BE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19790","DOI":"10.1039\/D0RA04199H","article-title":"Nature as a treasure trove of potential anti-SARS-CoV drug leads: A structural\/mechanistic rationale","volume":"10","author":"Sayed","year":"2020","journal-title":"RSC Adv."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3647","DOI":"10.1039\/D0CS01118E","article-title":"Antiviral drug discovery: Preparing for the next pandemic","volume":"50","author":"Adamson","year":"2021","journal-title":"Chem. 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