{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:11:21Z","timestamp":1787238681275,"version":"build-2736575974"},"reference-count":25,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T00:00:00Z","timestamp":1615766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>SARS-CoV-2 currently lacks effective first-line drug treatment. We present promising data from in silico docking studies of new Methisazone compounds (modified with calcium, Ca; iron, Fe; magnesium, Mg; manganese, Mn; or zinc, Zn) designed to bind more strongly to key proteins involved in replication of SARS-CoV-2. In this in silico molecular docking study, we investigated the inhibiting role of Methisazone and the modified drugs against SARS-CoV-2 proteins: ribonucleic acid (RNA)-dependent RNA polymerase (RdRp), spike protein, papain-like protease (PlPr), and main protease (MPro). We found that the highest binding interactions were found with the spike protein (6VYB), with the highest overall binding being observed with Mn-bound Methisazone at \u22128.3 kcal\/mol, followed by Zn and Ca at \u22128.0 kcal\/mol, and Fe and Mg at \u22127.9 kcal\/mol. We also found that the metal-modified Methisazone had higher affinity for PlPr and MPro. In addition, we identified multiple binding pockets that could be singly or multiply occupied on all proteins tested. The best binding energy was with Mn\u2013Methisazone versus spike protein, and the largest cumulative increases in binding energies were found with PlPr. We suggest that further studies are warranted to identify whether these compounds may be effective for treatment and\/or prophylaxis.<\/jats:p>","DOI":"10.3390\/ijms22062977","type":"journal-article","created":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T11:38:58Z","timestamp":1615808338000},"page":"2977","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Metal-Bound Methisazone; Novel Drugs Targeting Prophylaxis and Treatment of SARS-CoV-2, a Molecular Docking Study"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0473-9764","authenticated-orcid":false,"given":"Ahmed","family":"Abdelaal Ahmed Mahmoud M. Alkhatip","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Beni-Suef University, Beni Suef 62511, Egypt"},{"name":"Birmingham Children\u2019s Hospital, Birmingham B4 6NH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4425-9677","authenticated-orcid":false,"given":"Michail","family":"Georgakis","sequence":"additional","affiliation":[{"name":"Sinodos Chemistry Company (SinodosChemistry.com), Tenedou 16 str, 54453 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8456-0202","authenticated-orcid":false,"given":"Lucio R.","family":"Montero Valenzuela","sequence":"additional","affiliation":[{"name":"Instituto de Biotecnolog\u00eda, UNAM (ibt.unam.mx), 62210 Cuernavaca, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4427-6047","authenticated-orcid":false,"given":"Mohamed","family":"Hamza","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Cairo University, Giza 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2501-6511","authenticated-orcid":false,"given":"Ehab","family":"Farag","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Beni-Suef University, Beni Suef 62511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaqui","family":"Hodgkinson","sequence":"additional","affiliation":[{"name":"Jaqui Hodgkinson Communications, 3722JK Bilthoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6797-6989","authenticated-orcid":false,"given":"Hisham","family":"Hosny","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Cairo University, Giza 11562, Egypt"},{"name":"Essex Cardiothoracic Centre, MSE Foundation Trust, Basildon SS16 5NL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6741-7079","authenticated-orcid":false,"given":"Ahmed M.","family":"Kamal","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Cairo University, Giza 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8458-6464","authenticated-orcid":false,"given":"Mohamed","family":"Wagih","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Cairo University, Giza 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5433-3511","authenticated-orcid":false,"given":"Amr","family":"Naguib","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Cairo University, Giza 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6083-5697","authenticated-orcid":false,"given":"Hany","family":"Yassin","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Fayoum University, Faiyum 63514, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8778-018X","authenticated-orcid":false,"given":"Haytham","family":"Algameel","sequence":"additional","affiliation":[{"name":"Aberdeen Royal Infirmary Hospital, Aberdeen AB25 2ZN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6539-8123","authenticated-orcid":false,"given":"Mohamed","family":"Elayashy","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Cairo University, Giza 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Abdelhaq","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Cairo University, Giza 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3461-8717","authenticated-orcid":false,"given":"Mohamed I.","family":"Younis","sequence":"additional","affiliation":[{"name":"Cambridge University Hospital, Cambridge CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5328-6039","authenticated-orcid":false,"given":"Hassan","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Cairo University, Giza 11562, Egypt"},{"name":"Leeds General Infirmary Hospital, Leeds LS1 3EX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Abdulshafi","sequence":"additional","affiliation":[{"name":"Imam Abdulrahman Bin Faisal University Hospital, University of Dammam, Dammam 34221, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed A.","family":"Elramely","sequence":"additional","affiliation":[{"name":"National Cancer Institute, Cairo University, Giza 11796, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1001\/jama.2020.1585","article-title":"Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus\u2013infected pneumonia in Wuhan, China","volume":"323","author":"Wang","year":"2020","journal-title":"JAMA"},{"key":"ref_2","unstructured":"World Health Organization (2021, January 10). 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