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© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

A new severe acute respiratory syndrome coronavirus (SARS-CoV-2) causing coronavirus diseases 2019 (COVID-19), which emerged in Wuhan, China in December 2019, has spread worldwide. Currently, very few treatments are officially recommended against SARS-CoV-2. Identifying effective, low-cost antiviral drugs with limited side effects that are affordable immediately is urgently needed. Methylene blue, a synthesized thiazine dye, may be a potential antiviral drug. Antiviral activity of methylene blue used alone or in combination with several antimalarial drugs or remdesivir was assessed against infected Vero E6 cells infected with two clinically isolated SARS-CoV-2 strains (IHUMI-3 and IHUMI-6). Effects both on viral entry in the cell and on post-entry were also investigated. After 48 h post-infection, the viral replication was estimated by RT-PCR. The median effective concentration (EC50) and 90% effective concentration (EC90) of methylene blue against IHUMI-3 were 0.41 ± 0.34 µM and 1.85 ± 1.41 µM, respectively; 1.06 ± 0.46 µM and 5.68 ± 1.83 µM against IHUMI-6. Methylene blue interacted at both entry and post-entry stages of SARS-CoV-2 infection in Vero E6 cells as retrieved for hydroxychloroquine. The effects of methylene blue were additive with those of quinine, mefloquine and pyronaridine. The combinations of methylene blue with chloroquine, hydroxychloroquine, desethylamodiaquine, piperaquine, lumefantrine, ferroquine, dihydroartemisinin and remdesivir were antagonist. These results support the potential interest of methylene blue to treat COVID-19.

Details

Title
In Vitro Evaluation of the Antiviral Activity of Methylene Blue Alone or in Combination against SARS-CoV-2
Author
Gendrot, Mathieu 1   VIAFID ORCID Logo  ; Jardot, Priscilla 2 ; Delandre, Océane 1 ; Boxberger, Manon 2   VIAFID ORCID Logo  ; Andreani, Julien 2 ; Duflot, Isabelle 2 ; Marion Le Bideau 2 ; Mosnier, Joel 3 ; Fonta, Isabelle 3 ; Hutter, Sébastien 4 ; Bernard La Scola 2   VIAFID ORCID Logo  ; Pradines, Bruno 3   VIAFID ORCID Logo 

 Unité Parasitologie et Entomologie, Département Microbiologie et Maladies Infectieuses, Institut de Recherche Biomédicale des Armées, 13005 Marseille, France; ma.gendrot@laposte.net (M.G.); o.delandre@gmail.com (O.D.); joelmosnier@orange.fr (J.M.); isabelle.fonta.09@gmail.com (I.F.); Aix Marseille Univ, IRD, SSA, AP-HM, VITROME, 13005 Marseille, France; sebastien.hutter@univ-amu.fr; IHU Méditerranée Infection, 13005 Marseille, France; Priscilla.JARDOT@univ-amu.fr (P.J.); manon.boxberger@hotmail.fr (M.B.); miaguiabidou@gmail.com (J.A.); isabelle.duflot@etu.univ-amu.fr (I.D.); Marion.LE-BIDEAU@ap-hm.fr (M.L.B.); bernard.la-scola@univ-amu.fr (B.L.S.) 
 IHU Méditerranée Infection, 13005 Marseille, France; Priscilla.JARDOT@univ-amu.fr (P.J.); manon.boxberger@hotmail.fr (M.B.); miaguiabidou@gmail.com (J.A.); isabelle.duflot@etu.univ-amu.fr (I.D.); Marion.LE-BIDEAU@ap-hm.fr (M.L.B.); bernard.la-scola@univ-amu.fr (B.L.S.); Aix Marseille Univ, IRD, AP-HM, MEPHI, 13005 Marseille, France 
 Unité Parasitologie et Entomologie, Département Microbiologie et Maladies Infectieuses, Institut de Recherche Biomédicale des Armées, 13005 Marseille, France; ma.gendrot@laposte.net (M.G.); o.delandre@gmail.com (O.D.); joelmosnier@orange.fr (J.M.); isabelle.fonta.09@gmail.com (I.F.); Aix Marseille Univ, IRD, SSA, AP-HM, VITROME, 13005 Marseille, France; sebastien.hutter@univ-amu.fr; IHU Méditerranée Infection, 13005 Marseille, France; Priscilla.JARDOT@univ-amu.fr (P.J.); manon.boxberger@hotmail.fr (M.B.); miaguiabidou@gmail.com (J.A.); isabelle.duflot@etu.univ-amu.fr (I.D.); Marion.LE-BIDEAU@ap-hm.fr (M.L.B.); bernard.la-scola@univ-amu.fr (B.L.S.); Centre National de Référence du Paludisme, 13005 Marseille, France 
 Aix Marseille Univ, IRD, SSA, AP-HM, VITROME, 13005 Marseille, France; sebastien.hutter@univ-amu.fr; IHU Méditerranée Infection, 13005 Marseille, France; Priscilla.JARDOT@univ-amu.fr (P.J.); manon.boxberger@hotmail.fr (M.B.); miaguiabidou@gmail.com (J.A.); isabelle.duflot@etu.univ-amu.fr (I.D.); Marion.LE-BIDEAU@ap-hm.fr (M.L.B.); bernard.la-scola@univ-amu.fr (B.L.S.) 
First page
3007
Publication year
2021
Publication date
2021
Publisher
MDPI AG
e-ISSN
20770383
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2554573964
Copyright
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.