Methylene Blue has a potent antiviral activity against SARS-CoV-2 and H1N1 influenza virus in the absence of UV-activation in vitro

Abstract

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 degradation of genomic RNA is only observed in the presence of light and after long exposure. Our work supports the interest of testing methylene blue in clinical studies to confirm a preventive or therapeutic efficacy against both Influenza Virus H1N1 and SARS-CoV-2 infections.

Methylene Blue Is a Nonspecific Protein-Protein Interaction Inhibitor with Potential for Repurposing as an Antiviral for COVID-19

“…Finally, an image-based multicycle replication assay based repurposing screening of a chemical library of 5440 compounds that are approved, in clinical trial, or in preclinical development by Murer, Greber and coworkers at the University of Zurich (Zurich, Switzerland) identified MeBlu as one of two promising candidates (the other being mycophenolic acid) that have low micromolar activity against SARS-CoV-2 (1.4 μM). While Cagno et al reported a good therapeutic index for MeBlu in Vero E6 cell-based assay (TI = 46.1/0.11 = 420) [36], this study by Murer et al with Huh7 cells found it to be even lower (TI = 8.7/1.4 = 6.2) [41] than that obtained here with HEK293T cells (TI = 12–16).…”

“…For example, Cagno, Tapparel, and coworkers at the University of Geneva (Geneva, Switzerland) found that MeBlu showed preventive or therapeutic virucidal activity against SARS-CoV-2 (as well as influenza virus H1N1) at low micromolar concentrations and in the absence of UV-activation [36]. Their results also suggested that the antiviral activity of MeBlu might result from multiple mechanisms of action as the extent of genomic RNA degradation was higher in presence of light and after long exposure.…”