{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T15:34:26Z","timestamp":1768491266080,"version":"3.49.0"},"posted":{"date-parts":[[2020,7,15]]},"group-title":"Microbiology","reference-count":32,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2020,7,15]],"date-time":"2020-07-15T00:00:00Z","timestamp":1594771200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2020,7,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  With continued expansion of the COVID-19 pandemic, antiviral drugs are desperately needed to treat patients at high risk of life-threatening disease and even to limit spread if administered early during infection. Typically, the fastest route to identifying and licensing a safe and effective antiviral drug is to test those already shown safe in early clinical trials for other infections or diseases. Here, we tested\n                  <jats:italic>in vitro<\/jats:italic>\n                  oleandrin, derived from the\n                  <jats:italic>Nerium oleander<\/jats:italic>\n                  plant and shown previously to have inhibitory activity against several viruses. Using Vero cells, we found that prophylactic oleandrin administration at concentrations down to 0.05 \u03bcg\/ml exhibited potent antiviral activity against SARS-CoV-2, with an 800-fold reduction in virus production, and a 0.1 \u03bcg\/ml dose resulted in a greater than 3,000-fold reduction in infectious virus production. The EC\n                  <jats:sub>50<\/jats:sub>\n                  values were 11.98ng\/ml when virus output was measured at 24 hours post-infection, and 7.07ng\/ml measured at 48 hours post-infection. Therapeutic (post-infection) treatment up to 24 hours after infection of Vero cells also reduced viral titers, with the 0.1 \u03bcg\/ml dose causing greater than 100-fold reductions as measured at 48 hours, and the 0.05 \u03bcg\/ml dose resulting in a 78-fold reduction. The potent prophylactic and therapeutic antiviral activities demonstrated here strongly support the further development of oleandrin to reduce the severity of COVID-19 and potentially also to reduce spread by persons diagnosed early after infection.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>IMPORTANCE<\/jats:title>\n                  <jats:p>\n                    COVID-19, a pandemic disease caused by infection with SARS-CoV-2, has swept around the world to cause millions of infections and hundreds-of-thousands of deaths due to the lack of vaccines and effective therapeutics. We tested oleandrin, derived from the\n                    <jats:italic>Nerium oleander<\/jats:italic>\n                    plant and shown previously to reduce the replication of several viruses, against SARS-CoV-2 infection of Vero cells. When administered both before and after virus infection, nanogram doses of oleandrin significantly inhibited replication by up to 3,000-fold, indicating the potential to prevent disease and virus spread in persons recently exposed to SARS-CoV-2, as well as to prevent severe disease in persons at high risk. These results indicate that oleandrin should be tested in animal models and in humans exposed to infection to determine its medical usefulness in controlling the pandemic.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2020.07.15.203489","type":"posted-content","created":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T07:45:54Z","timestamp":1594885554000},"source":"Crossref","is-referenced-by-count":12,"title":["Prophylactic and Therapeutic Inhibition of In Vitro SARS-CoV-2 Replication by Oleandrin"],"prefix":"10.64898","author":[{"given":"Kenneth S.","family":"Plante","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica A.","family":"Plante","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana","family":"Fernandez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Divya","family":"Mirchandani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathen","family":"Bopp","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia V.","family":"Aguilar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. Jagannadha","family":"Sastry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert A.","family":"Newman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8016-8556","authenticated-orcid":false,"given":"Scott C.","family":"Weaver","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024080416011413000_2020.07.15.203489v1.1","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/S1473-3099(20)30076-1","article-title":"Outbreak of coronavirus disease 2019","volume":"20","year":"2020","journal-title":"Lancet Infect Dis"},{"key":"2024080416011413000_2020.07.15.203489v1.2","doi-asserted-by":"crossref","unstructured":"Matheny Antommaria AH , Gibb TS , McGuire AL , Wolpe PR , Wynia MK , Applewhite MK , Caplan A , Diekema DS , Hester DM , Lehmann LS , McLeod-Sordjan R , Schiff T , Tabor HK , Wieten SE , Eberl JT , and for a Task Force of the Association of Bioethics Program D. 2020. Ventilator Triage Policies During the COVID-19 Pandemic at U.S. Hospitals Associated With Members of the Association of Bioethics Program Directors. Ann Intern Med.","DOI":"10.7326\/M20-1738"},{"key":"2024080416011413000_2020.07.15.203489v1.3","doi-asserted-by":"crossref","unstructured":"Beigel JH , Tomashek KM , Dodd LE , Mehta AK , Zingman BS , Kalil AC , Hohmann E , Chu HY , Luetkemeyer A , Kline S , Lopez de Castilla D , Finberg RW , Dierberg K , Tapson V , Hsieh L , Patterson TF , Paredes R , Sweeney DA , Short WR , Touloumi G , Lye DC , Ohmagari N , Oh MD , Ruiz-Palacios GM , Benfield T , Fatkenheuer G , Kortepeter MG , Atmar RL , Creech CB , Lundgren J , Babiker AG , Pett S , Neaton JD , Burgess TH , Bonnett T , Green M , Makowski M , Osinusi A , Nayak S , Lane HC , Members A-SG. 2020. Remdesivir for the Treatment of Covid-19 - Preliminary Report. 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Antiviral Efficacies of FDA-Approved Drugs against SARS-CoV-2 Infection in Ferrets. mBio 11.","DOI":"10.1128\/mBio.01114-20"},{"key":"2024080416011413000_2020.07.15.203489v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2015.37"},{"key":"2024080416011413000_2020.07.15.203489v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(85)80458-7"},{"key":"2024080416011413000_2020.07.15.203489v1.11","first-page":"239","article-title":"Antioxidant, anti-inflammatory, anti-apoptotic, and skin regenerative properties of an Aloe vera-based extract of Nerium oleander leaves (nae-8((R)))","volume":"8","year":"2015","journal-title":"Clin Cosmet Investig Dermatol"},{"key":"2024080416011413000_2020.07.15.203489v1.12","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-014-0190-6"},{"key":"2024080416011413000_2020.07.15.203489v1.13","doi-asserted-by":"publisher","DOI":"10.1177\/1534735407309623"},{"key":"2024080416011413000_2020.07.15.203489v1.14","first-page":"167","article-title":"Oleandrin-mediated oxidative stress in human melanoma cells","volume":"5","year":"2006","journal-title":"J Exp Ther Oncol"},{"key":"2024080416011413000_2020.07.15.203489v1.15","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-014-0127-0"},{"key":"2024080416011413000_2020.07.15.203489v1.16","doi-asserted-by":"crossref","unstructured":"Amarelle L , Lecuona E. 2018. The Antiviral Effects of Na,K-ATPase Inhibition: A Minireview. Int J Mol Sci 19.","DOI":"10.3390\/ijms19082154"},{"key":"2024080416011413000_2020.07.15.203489v1.17","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.fitote.2012.10.017","article-title":"Nerium oleander derived cardiac glycoside oleandrin is a novel inhibitor of HIV infectivity","volume":"84","year":"2013","journal-title":"Fitoterapia"},{"key":"2024080416011413000_2020.07.15.203489v1.18","doi-asserted-by":"crossref","unstructured":"Hutchison T , Yapindi L , Malu A , Newman RA , Sastry KJ , Harrod R. 2019. The Botanical Glycoside Oleandrin Inhibits Human T-cell Leukemia Virus Type-1 Infectivity and Env-Dependent Virological Synapse Formation. 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