In Vitro Evaluation of the Antiviral Activity of Methylene Blue Alone or in Combination against SARS-CoV-2

Journal of Clinical Medicine

Sébastien Hutter¹  Isabelle Duflot²  Bernard La Scola²  Julien Andreani²  Manon Boxberger²  Priscilla Jardot²  Marion Le Bideau²  Isabelle Fonta³  Mathieu Gendrot³  Joel Mosnier³  Océane Delandre³  Bruno Pradines³ 

[1] Aix Marseille Univ, IRD, SSA, AP-HM, VITROME, 13005 Marseille, France;IHU Méditerranée Infection, 13005 Marseille, France;Unité Parasitologie et Entomologie, Département Microbiologie et Maladies Infectieuses, Institut de Recherche Biomédicale des Armées, 13005 Marseille, France;

关键词: COVID-19;    SARS-CoV-2;    antiviral;    in vitro;    methylene blue;    antimalarial drug;   

DOI  :  10.3390/jcm10143007

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown