{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:27:48Z","timestamp":1790011668771,"version":"4.0.1"},"reference-count":71,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T00:00:00Z","timestamp":1626134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003009","name":"Science and Technology Development Fund","doi-asserted-by":"publisher","award":["5480"],"award-info":[{"award-number":["5480"]}],"id":[{"id":"10.13039\/501100003009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003009","name":"Science and Technology Development Fund","doi-asserted-by":"publisher","award":["7972"],"award-info":[{"award-number":["7972"]}],"id":[{"id":"10.13039\/501100003009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007446","name":"King Khalid University","doi-asserted-by":"publisher","award":["R.G.P.1\/143\/42"],"award-info":[{"award-number":["R.G.P.1\/143\/42"]}],"id":[{"id":"10.13039\/501100007446","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>The coronavirus pandemic has affected more than 150 million people, while over 3.25 million people have died from the coronavirus disease 2019 (COVID-19). As there are no established therapies for COVID-19 treatment, drugs that inhibit viral replication are a promising target; specifically, the main protease (Mpro) that process CoV-encoded polyproteins serves as an Achilles heel for assembly of replication-transcription machinery as well as down-stream viral replication. In the search for potential antiviral drugs that target Mpro, a series of cembranoid diterpenes from the biologically active soft-coral genus Sarcophyton have been examined as SARS-CoV-2 Mpro inhibitors. Over 360 metabolites from the genus were screened using molecular docking calculations. Promising diterpenes were further characterized by molecular dynamics (MD) simulations based on molecular mechanics-generalized Born surface area (MM-GBSA) binding energy calculations. According to in silico calculations, five cembranoid diterpenes manifested adequate binding affinities as Mpro inhibitors with \u0394Gbinding &lt; \u221233.0 kcal\/mol. Binding energy and structural analyses of the most potent Sarcophyton inhibitor, bislatumlide A (340), was compared to darunavir, an HIV protease inhibitor that has been recently subjected to clinical-trial as an anti-COVID-19 drug. In silico analysis indicates that 340 has a higher binding affinity against Mpro than darunavir with \u0394Gbinding values of \u221243.8 and \u221234.8 kcal\/mol, respectively throughout 100 ns MD simulations. Drug-likeness calculations revealed robust bioavailability and protein-protein interactions were identified for 340; biochemical signaling genes included ACE, MAPK14 and ESR1 as identified based on a STRING database. Pathway enrichment analysis combined with reactome mining revealed that 340 has the capability to re-modulate the p38 MAPK pathway hijacked by SARS-CoV-2 and antagonize injurious effects. These findings justify further in vivo and in vitro testing of 340 as an antiviral agent against SARS-CoV-2.<\/jats:p>","DOI":"10.3390\/md19070391","type":"journal-article","created":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T22:25:31Z","timestamp":1626215131000},"page":"391","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Blue Biotechnology: Computational Screening of Sarcophyton Cembranoid Diterpenes for SARS-CoV-2 Main Protease Inhibition"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4819-2040","authenticated-orcid":false,"given":"Mahmoud A. A.","family":"Ibrahim","sequence":"first","affiliation":[{"name":"Computational Chemistry Laboratory, Chemistry Department, Faculty of Science, Minia University, Minia 61519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3527-0126","authenticated-orcid":false,"given":"Alaa H. M.","family":"Abdelrahman","sequence":"additional","affiliation":[{"name":"Computational Chemistry Laboratory, Chemistry Department, Faculty of Science, Minia University, Minia 61519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2462-1269","authenticated-orcid":false,"given":"Mohamed A. M.","family":"Atia","sequence":"additional","affiliation":[{"name":"Molecular Genetics and Genome Mapping Laboratory, Genome Mapping Department, Agricultural Genetic Engineering Research Institute (AGERI), Agricultural Research Center (ARC), Giza 12619, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1639-3518","authenticated-orcid":false,"given":"Tarik A.","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Chemistry of Medicinal Plants Department, National Research Centre, 33 El-Bohouth St., Dokki, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud F.","family":"Moustafa","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, King Khalid University, Abha 9004, Saudi Arabia"},{"name":"Department of Botany & Microbiology, Faculty of Science, South Valley University, Qena 83523, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2101-8800","authenticated-orcid":false,"given":"Abdulrahim R.","family":"Hakami","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha 61481, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaden A. M.","family":"Khalifa","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, S-106 91 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0151-8309","authenticated-orcid":false,"given":"Fahad A.","family":"Alhumaydhi","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0850-5500","authenticated-orcid":false,"given":"Faris","family":"Alrumaihi","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9497-0902","authenticated-orcid":false,"given":"Syed Hani","family":"Abidi","sequence":"additional","affiliation":[{"name":"Department of Biological and Biomedical Sciences, Aga Khan University, Karachi 74800, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6486-9835","authenticated-orcid":false,"given":"Khaled S.","family":"Allemailem","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Efferth","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud E.","family":"Soliman","sequence":"additional","affiliation":[{"name":"Molecular Modelling and Drug Design Research Group, School of Health Sciences, University of KwaZulu-Natal, Westville, Durban 4000, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1644-723X","authenticated-orcid":false,"given":"Paul W.","family":"Par\u00e9","sequence":"additional","affiliation":[{"name":"Department of Chemistry & Biochemistry, Texas Tech University, Lubbock, TX 79409, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2519-6690","authenticated-orcid":false,"given":"Hesham R.","family":"El-Seedi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, El-Menoufia University, Shebin El-Kom 32512, Egypt"},{"name":"International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China"},{"name":"Pharmacognosy Group, Department of Pharmaceutical Biosciences, Uppsala University, Biomedical Centre, Box 574, 751 23 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0343-4969","authenticated-orcid":false,"given":"Mohamed-Elamir F.","family":"Hegazy","sequence":"additional","affiliation":[{"name":"Chemistry of Medicinal Plants Department, National Research Centre, 33 El-Bohouth St., Dokki, Giza 12622, Egypt"},{"name":"Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4939-2438-7_1","article-title":"Coronaviruses: An overview of their replication and pathogenesis","volume":"1282","author":"Fehr","year":"2015","journal-title":"Methods Mol. 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