{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T20:50:16Z","timestamp":1786740616103,"version":"build-2736575974"},"reference-count":27,"publisher":"American Chemical Society (ACS)","issue":"6","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-001"},{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-009"},{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"}],"funder":[{"name":"Sylvester Comprehensive Cancer Center, University of Miami"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,12,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>There is urgent therapeutic need for COVID-19, a disease for which there are currently no widely effective approved treatments and the emergency use authorized drugs do not result in significant and widespread patient improvement. The food and drug administration-approved drug ivermectin has long been shown to be both antihelmintic agent and a potent inhibitor of viruses such as Yellow Fever Virus. In this study, we highlight the potential of ivermectin packaged in an orally administrable nanoparticle that could serve as a vehicle to deliver a more potent therapeutic antiviral dose and demonstrate its efficacy to decrease expression of viral spike protein and its receptor angiotensin-converting enzyme 2 (ACE2), both of which are keys to lowering disease transmission rates. We also report that the targeted nanoparticle delivered ivermectin is able to inhibit the nuclear transport activities mediated through proteins such as importin \u03b1\/\u03b21 heterodimer as a possible mechanism of action. This study sheds light on ivermectin-loaded, orally administrable, biodegradable nanoparticles to be a potential treatment option for the novel coronavirus through a multilevel inhibition. As both ACE2 targeting and the presence of spike protein are features shared among this class of virus, this platform technology has the potential to serve as a therapeutic tool not only for COVID-19 but for other coronavirus strains as well.<\/jats:p>","DOI":"10.1021\/acsptsci.0c00179","type":"journal-article","created":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T09:20:14Z","timestamp":1606814414000},"page":"1371-1380","source":"Crossref","is-referenced-by-count":36,"title":["Clinically Approved\nAntiviral Drug in an Orally Administrable\nNanoparticle for COVID-19"],"prefix":"10.1021","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5997-3120","authenticated-orcid":true,"given":"Bapurao","family":"Surnar","sequence":"first","affiliation":[{"name":"University of Miami , , 1011 NW 15th Street , , ,","place":["Miami, Florida, United\nStates, 33136"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Z.","family":"Kamran","sequence":"additional","affiliation":[{"name":"University of Miami , , 1011 NW 15th Street , , ,","place":["Miami, Florida, United\nStates, 33136"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anuj S.","family":"Shah","sequence":"additional","affiliation":[{"name":"University of Miami , , 1011 NW 15th Street , , ,","place":["Miami, Florida, United\nStates, 33136"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3042-5272","authenticated-orcid":true,"given":"Shanta","family":"Dhar","sequence":"additional","affiliation":[{"name":"University of Miami , , 1011 NW 15th Street , , ,","place":["Miami, Florida, United\nStates, 33136"]},{"name":"University of Miami , , 1011 NW 15th Street , , ,","place":["Miami, Florida, United\nStates, 33136"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,12,1]]},"reference":[{"issue":"2","key":"2026081416171859800_cit1","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.jpha.2020.03.001","article-title":"Molecular\nimmune pathogenesis and diagnosis of COVID-19","volume":"10","author":"Li","year":"2020","journal-title":"J. Pharm. Anal."},{"key":"2026081416171859800_cit2","doi-asserted-by":"publisher","first-page":"108427","DOI":"10.1016\/j.clim.2020.108427","article-title":"COVID-19 pathophysiology:\nA review","volume":"215","author":"Yuki","year":"2020","journal-title":"Clin. Immunol."},{"issue":"10","key":"2026081416171859800_cit3","doi-asserted-by":"publisher","first-page":"1456","DOI":"10.1161\/CIRCRESAHA.120.317015","article-title":"Angiotensin-Converting\nEnzyme 2: SARS-CoV-2 Receptor and Regulator of the Renin-Angiotensin\nSystem","volume":"126","author":"Gheblawi","year":"2020","journal-title":"Circ. Res."},{"key":"2026081416171859800_cit4","doi-asserted-by":"publisher","first-page":"102463","DOI":"10.1016\/j.jaut.2020.102463","article-title":"Assessing ACE2 expression\npatterns in lung tissues in the pathogenesis of COVID-19","volume":"112","author":"Li","year":"2020","journal-title":"J. Autoimmun."},{"issue":"6","key":"2026081416171859800_cit5","doi-asserted-by":"publisher","first-page":"102537","DOI":"10.1016\/j.autrev.2020.102537","article-title":"The Role of\nCytokines including Interleukin-6 in COVID-19 induced Pneumonia and\nMacrophage Activation Syndrome-Like Disease","volume":"19","author":"McGonagle","year":"2020","journal-title":"Autoimmun. Rev."},{"issue":"6","key":"2026081416171859800_cit6","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1038\/s41577-020-0331-4","article-title":"Pathological inflammation in patients\nwith COVID-19:\na key role for monocytes and macrophages","volume":"20","author":"Merad","year":"2020","journal-title":"Nat.\nRev. Immunol."},{"key":"2026081416171859800_cit7","doi-asserted-by":"publisher","first-page":"1620","DOI":"10.1038\/s41467-020-15562-9","article-title":"Characterization of\nspike glycoprotein\nof SARS-CoV-2 on virus entry and its immune cross-reactivity with\nSARS-CoV","volume":"11","author":"Ou","year":"2020","journal-title":"Nat. Commun."},{"key":"2026081416171859800_cit8","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1093\/cid\/ciaa248","article-title":"Dysregulation of immune response in patients with COVID-19\nin Wuhan, China","volume":"71","author":"Qin","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"2026081416171859800_cit9","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1038\/s41591-020-0868-6","article-title":"SARS-CoV-2\nentry factors are highly expressed in nasal epithelial cells together\nwith innate immune genes","volume":"26","author":"Sungnak","year":"2020","journal-title":"Nat. Med."},{"issue":"6485","key":"2026081416171859800_cit10","doi-asserted-by":"publisher","first-page":"1444","DOI":"10.1126\/science.abb2762","article-title":"Structural basis for the recognition\nof SARS-CoV-2 by full-length\nhuman ACE2","volume":"367","author":"Yan","year":"2020","journal-title":"Science"},{"issue":"4","key":"2026081416171859800_cit11","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1007\/s00134-020-05985-9","article-title":"Angiotensin-converting\nenzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and\npotential therapeutic target","volume":"46","author":"Zhang","year":"2020","journal-title":"Intensive Care\nMed."},{"issue":"1","key":"2026081416171859800_cit12","doi-asserted-by":"publisher","first-page":"7981","DOI":"10.33263\/BRIAC111.79817993","article-title":"Screening of Potent Inhibitors Against 2019 Novel Coronavirus\n(Covid-19) from Alliumsativum and Allium cepa: An In Silico\nApproach","volume":"11","author":"Pandey","year":"2021","journal-title":"Biointerface Res. Appl. Chem."},{"issue":"1","key":"2026081416171859800_cit13","doi-asserted-by":"publisher","first-page":"8482","DOI":"10.33263\/BRIAC111.84828501","article-title":"A Drug Repurposing Approach Towards\nElucidating the Potential of Flavonoids as COVID-19 Spike Protein\nInhibitors","volume":"11","author":"Pandey","year":"2021","journal-title":"Biointerface Res. Appl. Chem."},{"issue":"8","key":"2026081416171859800_cit14","doi-asserted-by":"publisher","first-page":"1884","DOI":"10.1093\/jac\/dks147","article-title":"Ivermectin Is a Potent\nInhibitor of Flavivirus Replication Specifically Targeting NS3 Helicase\nActivity: New Prospects for an Old Drug","volume":"67","author":"Mastrangelo","year":"2012","journal-title":"J.\nAntimicrob. Chemother."},{"issue":"9","key":"2026081416171859800_cit15","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1038\/s41429-020-0336-z","article-title":"Ivermectin:\na systematic review from antiviral effects\nto COVID-19 complementary regimen","volume":"73","author":"Heidary","year":"2020","journal-title":"J. Antibiot."},{"key":"2026081416171859800_cit16","doi-asserted-by":"publisher","first-page":"124","DOI":"10.3389\/fmicb.2016.00124","article-title":"The Pseudorabies Virus DNA Polymerase\nAccessory Subunit UL42 Directs Nuclear Transport of the Holoenzyme","volume":"7","author":"Wang","year":"2016","journal-title":"Front. Microbiol."},{"key":"2026081416171859800_cit17","doi-asserted-by":"publisher","first-page":"11034","DOI":"10.1021\/acsnano.9b02807","article-title":"Orally Administrable\nTherapeutic Synthetic Nanoparticle for Zika Virus","volume":"13","author":"Surnar","year":"2019","journal-title":"ACS Nano"},{"issue":"2","key":"2026081416171859800_cit18","first-page":"79","article-title":"Ivermectin\nuptake and distribution in the plasma and tissue of Sudanese and Mexican\npatients infected with Onchocerca volvulus","volume":"42","author":"Elkassaby","year":"1991","journal-title":"Trop. Med. Parasitol."},{"issue":"6","key":"2026081416171859800_cit19","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1016\/j.ajog.2020.03.021","article-title":"Coronavirus\ndisease 2019 (COVID-19) pandemic and pregnancy","volume":"222","author":"Dashraath","year":"2020","journal-title":"Am. J. Obstet. Gynecol."},{"key":"2026081416171859800_cit20","doi-asserted-by":"publisher","first-page":"104787","DOI":"10.1016\/j.antiviral.2020.104787","article-title":"The FDA-approved\ndrug ivermectin inhibits the replication of SARS-CoV-2 in\nvitro","volume":"179","author":"Caly","year":"2020","journal-title":"Antiviral Res."},{"issue":"17","key":"2026081416171859800_cit21","doi-asserted-by":"publisher","first-page":"11507","DOI":"10.1128\/JVI.79.17.11507-11512.2005","article-title":"Intracellular localization\nof the severe acute respiratory\nsyndrome coronavirus nucleocapsid protein: absence of nucleolar accumulation\nduring infection and after expression as a recombinant protein in\nVero cells","volume":"79","author":"Rowland","year":"2005","journal-title":"J. Virol."},{"issue":"1\u20132","key":"2026081416171859800_cit22","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.virusres.2005.05.007","article-title":"Nuclear\/nucleolar\nlocalization properties of C-terminal\nnucleocapsid protein of SARS coronavirus","volume":"114","author":"Timani","year":"2005","journal-title":"Virus\nRes."},{"issue":"2","key":"2026081416171859800_cit23","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1177\/1087057110390360","article-title":"An AlphaScreen\u00ad(R)-based\nassay for high-throughput screening for specific inhibitors of nuclear\nimport","volume":"16","author":"Wagstaff","year":"2011","journal-title":"J. Biomol. 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Microbiol."},{"key":"2026081416171859800_cit26","doi-asserted-by":"publisher","first-page":"104760","DOI":"10.1016\/j.antiviral.2020.104760","article-title":"The broad spectrum antiviral ivermectin\ntargets the host nuclear transport importin alpha\/beta1 heterodimer","volume":"177","author":"Yang","year":"2020","journal-title":"Antiviral Res."},{"issue":"2","key":"2026081416171859800_cit27","doi-asserted-by":"publisher","first-page":"C258","DOI":"10.1152\/ajpcell.00224.2020","article-title":"Decoding SARS-CoV-2\nhijacking of host mitochondria in COVID-19 pathogenesis","volume":"319","author":"Singh","year":"2020","journal-title":"Am. J. 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