{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:03:57Z","timestamp":1760148237500,"version":"build-2065373602"},"reference-count":56,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T00:00:00Z","timestamp":1681257600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000871","name":"Department of Medicine, Mayo Clinic Florida","doi-asserted-by":"publisher","award":["STARDOM #94551013"],"award-info":[{"award-number":["STARDOM #94551013"]}],"id":[{"id":"10.13039\/100000871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We have previously shown computationally that Mycolactone (MLN), a toxin produced by Mycobacterium ulcerans, strongly binds to Munc18b and other proteins, presumably blocking degranulation and exocytosis of blood platelets and mast cells. We investigated the effect of MLN on endocytosis using similar approaches, and it bound strongly to the N-terminal of the clathrin protein and a novel SARS-CoV-2 fusion protein. Experimentally, we found 100% inhibition up to 60 nM and 84% average inhibition at 30 nM in SARS-CoV-2 live viral assays. MLN was also 10\u00d7 more potent than remdesivir and molnupiravir. MLN\u2019s toxicity against human alveolar cell line A549, immortalized human fetal renal cell line HEK293, and human hepatoma cell line Huh7.1 were 17.12%, 40.30%, and 36.25%, respectively. The cytotoxicity IC50 breakpoint ratio versus anti-SARS-CoV-2 activity was more than 65-fold. The IC50 values against the alpha, delta, and Omicron variants were all below 0.020 \u00b5M, and 134.6 nM of MLN had 100% inhibition in an entry and spread assays. MLN is eclectic in its actions through its binding to Sec61, AT2R, and the novel fusion protein, making it a good drug candidate for treating and preventing COVID-19 and other similarly transmitted enveloped viruses and pathogens.<\/jats:p>","DOI":"10.3390\/ijms24087151","type":"journal-article","created":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T02:29:15Z","timestamp":1681352955000},"page":"7151","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mycolactone: A Broad Spectrum Multitarget Antiviral Active in the Picomolar Range for COVID-19 Prevention and Cure"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2585-1800","authenticated-orcid":false,"given":"Seth Osei","family":"Asiedu","sequence":"first","affiliation":[{"name":"Department of Parasitology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Accra P.O. Box GA 337, Ghana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3002-1315","authenticated-orcid":false,"given":"Yash","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vlad","family":"Nicolaescu","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Ricketts Laboratory, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haley","family":"Gula","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Ricketts Laboratory, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1055-3069","authenticated-orcid":false,"given":"Thomas R.","family":"Caulfield","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Division of QHS Computational Biology, Mayo Clinic, Jacksonville, FL 32224, USA"},{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ravi","family":"Durvasula","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2901-0339","authenticated-orcid":false,"given":"Prakasha","family":"Kempaiah","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1093-1517","authenticated-orcid":false,"given":"Samuel K.","family":"Kwofie","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, School of Engineering, University of Ghana, Legon, Accra P.O. Box 77, Ghana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6048-8509","authenticated-orcid":false,"given":"Michael D.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Accra P.O. Box GA 337, Ghana"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.ijid.2020.01.009","article-title":"The Continuing 2019-NCoV Epidemic Threat of Novel Coronaviruses to Global Health\u2014The Latest 2019 Novel Coronavirus Outbreak in Wuhan, China","volume":"91","author":"Hui","year":"2020","journal-title":"Int. J. Infect. Dis."},{"key":"ref_2","unstructured":"(2022, September 14). WHO Weekly Epidemiological Update on COVID-19\u201414 September 2022. 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