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

Valeria Cagno,Arnaud Charles-Antoine Zwygart,Andreas Cerny,Thomas Cerny,Caroline Tapparel,Chiara Medaglia,Erich Cerny

doi:10.1038/s41598-021-92481-9

Valeria Cagno, Arnaud Charles-Antoine Zwygart + Show 5 more

Open Access

https://doi.org/10.1038/s41598-021-92481-9

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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 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.

Highlights

Methylene blue is an FDA (Food and Drug Administration) and EMA (European Medicines Agency) approved drug with an excellent safety profile
Our findings reveal that methylene blue displays virucidal preventive or therapeutic activity against influenza virus H1N1 and SARSCoV-2 at low micromolar concentrations and in the absence of UV-activation
The reduction of H1N1 infectiousness induced by Methylene Blue (MB) did not always result in a reduction of viral genome quantified by RT-qPCR

Summary

Introduction

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. 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 against SARS-CoV-2. Neuraminidase treatment has been shown to increase the affinity of SARS-CoV-2 for its receptor, ACE-2, and this might increase the susceptibility of influenza infected patients to SARS-CoV-2 superinfection[2] This scenario highlights the urgent clinical need for broad-spectrum antiviral drugs ready to use during pandemics and epidemics. Sensitivity to thiazine dyes and glucose 6 phosphate dehydrogenase deficiency are c ontraindications[10]

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