{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T17:50:57Z","timestamp":1779213057555,"version":"3.51.4"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,7,12]],"date-time":"2021-07-12T00:00:00Z","timestamp":1626048000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,7,12]],"date-time":"2021-07-12T00:00:00Z","timestamp":1626048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Fondation des HUG"},{"name":"Carigest Foundation"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Methylene blue is an FDA (Food and Drug Administration) and EMA (European Medicines Agency) approved drug with an excellent safety profile. It displays broad-spectrum virucidal activity in the presence of UV light and has been shown to be effective in inactivating various viruses in blood products prior to transfusions. In addition, its use has been validated for methemoglobinemia and malaria treatment. In this study, we first evaluated the virucidal activity of methylene blue against influenza virus H1N1 upon different incubation times and in the presence or absence of light activation, and then against SARS-CoV-2. We further assessed the therapeutic activity of methylene blue by administering it to cells previously infected with SARS-CoV-2. Finally, we examined the effect of co-administration of the drug together with immune serum. Our findings reveal that methylene blue displays virucidal preventive or therapeutic activity against influenza virus H1N1 and SARS-CoV-2 at low micromolar concentrations and in the absence of UV-activation. We also confirm that MB antiviral activity is based on several mechanisms of action as the extent of genomic RNA degradation is higher in presence of light and after long exposure. Our work supports the interest of testing methylene blue in clinical studies to confirm a preventive and\/or therapeutic efficacy against both influenza virus H1N1 and SARS-CoV-2 infections.<\/jats:p>","DOI":"10.1038\/s41598-021-92481-9","type":"journal-article","created":{"date-parts":[[2021,7,12]],"date-time":"2021-07-12T06:03:06Z","timestamp":1626069786000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Methylene Blue has a potent antiviral activity against SARS-CoV-2 and H1N1 influenza virus in the absence of UV-activation in vitro"],"prefix":"10.1038","volume":"11","author":[{"given":"Valeria","family":"Cagno","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Medaglia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Cerny","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Cerny","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arnaud Charles-Antoine","family":"Zwygart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erich","family":"Cerny","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Tapparel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,7,12]]},"reference":[{"key":"92481_CR1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.26260","author":"C Yu","year":"2020","unstructured":"Yu, C. et al. Lopinavir\/ritonavir is associated with pneumonia resolution in COVID-19 patients with influenza coinfection: A retrospective matched-pair cohort study. J. Med. Virol. https:\/\/doi.org\/10.1002\/jmv.26260 (2020).","journal-title":"J. Med. Virol."},{"key":"92481_CR2","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1038\/s41467-020-20457-w","volume":"12","author":"H Chu","year":"2021","unstructured":"Chu, H. et al. Host and viral determinants for efficient SARS-CoV-2 infection of the human lung. Nat. Commun. 12, 134. https:\/\/doi.org\/10.1038\/s41467-020-20457-w (2021).","journal-title":"Nat. Commun."},{"key":"92481_CR3","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics10040223","author":"ME Nedu","year":"2020","unstructured":"Nedu, M. E., Tertis, M., Cristea, C. & Georgescu, A. V. Comparative study regarding the properties of methylene blue and proflavine and their optimal concentrations for in vitro and in vivo applications. Diagnostics https:\/\/doi.org\/10.3390\/diagnostics10040223 (2020).","journal-title":"Diagnostics"},{"key":"92481_CR4","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1002\/1096-9071(200012)62:4<421::AID-JMV5>3.0.CO;2-9","volume":"62","author":"T Owada","year":"2000","unstructured":"Owada, T. et al. Elucidation of the HIV-1 virucidal mechanism of methylene blue photosensitization and the effect on primary isolates. J. Med. Virol. 62, 421\u2013425 (2000).","journal-title":"J. Med. Virol."},{"key":"92481_CR5","doi-asserted-by":"publisher","first-page":"2202","DOI":"10.1111\/trf.14652","volume":"58","author":"M Eickmann","year":"2018","unstructured":"Eickmann, M. et al. Inactivation of Ebola virus and Middle East respiratory syndrome coronavirus in platelet concentrates and plasma by ultraviolet C light and methylene blue plus visible light, respectively. Transfusion 58, 2202\u20132207. https:\/\/doi.org\/10.1111\/trf.14652 (2018).","journal-title":"Transfusion"},{"key":"92481_CR6","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1186\/s12879-021-05993-0","volume":"21","author":"C Jin","year":"2021","unstructured":"Jin, C. et al. Methylene blue photochemical treatment as a reliable SARS-CoV-2 plasma virus inactivation method for blood safety and convalescent plasma therapy for COVID-19. BMC Infect. Dis. 21, 357. https:\/\/doi.org\/10.1186\/s12879-021-05993-0 (2021).","journal-title":"BMC Infect. Dis."},{"key":"92481_CR7","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1111\/j.1423-0410.1991.tb00907.x","volume":"60","author":"B Lambrecht","year":"1991","unstructured":"Lambrecht, B., Mohr, H., Knuver-Hopf, J. & Schmitt, H. Photoinactivation of viruses in human fresh plasma by phenothiazine dyes in combination with visible light. Vox Sang 60, 207\u2013213. https:\/\/doi.org\/10.1111\/j.1423-0410.1991.tb00907.x (1991).","journal-title":"Vox Sang"},{"key":"92481_CR8","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1111\/j.1751-1097.1998.tb05209.x","volume":"67","author":"JE Schneider Jr","year":"1998","unstructured":"Schneider, J. E. Jr. et al. Potential mechanisms of photodynamic inactivation of virus by methylene blue. I. RNA-protein crosslinks and other oxidative lesions in Q beta bacteriophage. Photochem. Photobiol. 67, 350\u2013357 (1998).","journal-title":"Photochem. Photobiol."},{"key":"92481_CR9","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1002\/jmv.1890470211","volume":"47","author":"B Bachmann","year":"1995","unstructured":"Bachmann, B., Knuver-Hopf, J., Lambrecht, B. & Mohr, H. Target structures for HIV-1 inactivation by methylene blue and light. J. Med. Virol. 47, 172\u2013178. https:\/\/doi.org\/10.1002\/jmv.1890470211 (1995).","journal-title":"J. Med. 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Repurposed antiviral drugs for COVID-19: Interim WHO SOLIDARITY trial results. medRxiv https:\/\/doi.org\/10.1101\/2020.10.15.20209817 (2020).","journal-title":"medRxiv"},{"key":"92481_CR13","doi-asserted-by":"publisher","DOI":"10.13128\/Substantia-888","author":"M Henry","year":"2020","unstructured":"Henry, M., Summa, M., Patrick, L. & Schwartz, L. A cohort of cancer patients with no reported cases of SARS-CoV-2 infection: The possible preventive role of Methylene Blue. Substantia https:\/\/doi.org\/10.13128\/Substantia-888 (2020).","journal-title":"Substantia"},{"key":"92481_CR14","doi-asserted-by":"publisher","DOI":"10.1101\/2020.08.29.273441","author":"D Bojadzic","year":"2020","unstructured":"Bojadzic, D., Alcazar, O. & Buchwald, P. 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The other authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"14295"}}