{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T18:55:04Z","timestamp":1789844104245,"version":"4.0.1"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,1,4]],"date-time":"2022-01-04T00:00:00Z","timestamp":1641254400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp; Biodiversity"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) replication depends on the interaction between the viral proteins and the human translation machinery. The cytotoxic peptide plitidepsin was found to inhibit CoV\u20102 up to 90\u2009% at a concentration of 0.88\u2005nM. <jats:italic>In vitro<\/jats:italic> studies suggest that this activity may be attributed to the inhibition of the eukaryotic translation elongation factor 1A (eEF1A). However, recent reports raised the potential for other cellular targets which plitidepsin may use to exert its potent antiviral activity. The lack of data about these potential targets represents a major limitation for its structural optimization. This work describes the use of a molecular modeling approach to rationalize the <jats:italic>in\u2005vitro<\/jats:italic> antiviral activity of plitidepsin and to identify potential cellular targets. The developed protocol involves an initial molecular docking step followed by molecular dynamics and binding free energy calculations. The results reveal the potential for plitidepsin to bind to the active site of the key enzyme SARS\u2010CoV\u20102 RdRp. The results also highlight the importance of <jats:italic>van der Waals<\/jats:italic> interactions for proper binding with the enzyme. We believe that the results presented in this study could provide the grounds for the optimization of plitidepsin analogs as SARS\u2010CoV\u20102 inhibitors.<\/jats:p>","DOI":"10.1002\/cbdv.202100719","type":"journal-article","created":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T14:50:01Z","timestamp":1637679001000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Computational Prediction of the Potential Target of SARS\u2010CoV\u20102 Inhibitor Plitidepsin via Molecular Docking, Dynamic Simulations and MM\u2010PBSA Calculations"],"prefix":"10.1002","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6795-4816","authenticated-orcid":false,"given":"Mahmoud A.","family":"El Hassab","sequence":"first","affiliation":[{"name":"Department of medicinal Chemistry Faculty of Pharmacy King Salman international University (KSIU)  South Sinai Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loah R.","family":"Hemeda","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry Faculty of Pharmacy Beni-Suef University  Beni-Suef 62514 Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zainab M.","family":"Elsayed","sequence":"additional","affiliation":[{"name":"Scientific research and innovation support unit Faculty of Pharmacy Kafrelsheikh University  Kafrelsheikh P.O. Box33516 Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara T.","family":"Al\u2010Rashood","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry College of Pharmacy King Saud University  P.O. Box 2457 Riyadh 11451 Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed K.","family":"Abdel\u2010Hamid Amin","sequence":"additional","affiliation":[{"name":"South Metropolitan Health Service  Murdoch WA 6150 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hatem A.","family":"Abdel\u2010Aziz","sequence":"additional","affiliation":[{"name":"Department of Applied Organic Chemistry National Research Center  Dokki, Giza P.O. Box 12622 Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wagdy M.","family":"Eldehna","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Faculty of Pharmacy Kafrelsheikh University  Kafrelsheikh P.O. Box 33516 Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,1,4]]},"reference":[{"key":"e_1_2_8_1_1","unstructured":"Update on the prevalence and control of novel coronavirus-induced pneumonia as of 24:00 on February 21.http:\/\/www.nhc.gov.cn\/xcs\/yqtb\/202002\/543cc508978a48d2b9322bdc83daa6fd.shtml(accessed February 23 2020) (in Chinese)."},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.2014P7"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2020.04.009"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2016.03.003"},{"key":"e_1_2_8_5_1","unstructured":"WHO (2020).\u2019Solidarity\u2019 clinical trial for COVID-19 treatments."},{"key":"e_1_2_8_6_1","article-title":"\u2018Pre-clinical search of SARS-CoV-2 inhibitors and their combinations in approved drugs to tackle COVID-19 pandemic\u2019","author":"Rodon J.","year":"2020","journal-title":"BioRxiv."},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13940-6"},{"key":"e_1_2_8_8_1","first-page":"992","article-title":"\u2018Remdesivir for the Treatment of Covid-19\u2014Preliminary Report\u2019","volume":"10","author":"Beigel J. 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Galmarini \u2018Translation elongation factor eEF1A2 is a novel anticancer target for the marine natural product plitidepsin\u2032 Scientific reports2016 6 1\u201315.","DOI":"10.1038\/srep35100"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201505069"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.10222"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abe9403"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2286-9"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abf4058"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.10222"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2020.1757510"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.20944\/preprints202003.0226.v1"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.26434\/chemrxiv.11831103.v1"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa216"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15092"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.softx.2015.06.001"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/ct700301q"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2020.584894"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2021.1885396"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1RA01809D"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/pr9061004"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/jp807056c"},{"key":"e_1_2_8_32_1","first-page":"p1","article-title":"\u2018Identification of bioactive molecules from Tea plant as SARS-CoV-2 main protease inhibitors\u2019","volume":"8","author":"Bhardwaj V. 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