In December 2019, a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus diseases 2019 (COVID-19) emerged in Wuhan, China. Currently there is no antiviral treatment recommended against SARS-CoV-2. Identifying effective antiviral drugs is urgently required. Methylene blue has already demonstrated in vitro antiviral activity in photodynamic therapy as well as antibacterial, antifungal and antiparasitic activities in non-photodynamic assays. In this study. non-photoactivated methylene blue showed in vitro activity at very low micromolar range with an EC_{50} (median effective concentration) of 0.30 ± 0.03 μM and an EC_{90} (90% effective concentration) of 0.75 ± 0.21 μM at a multiplicity of infection (MOI) of 0.25 against SARS-CoV-2 (strain IHUMI-3). The EC_{50} and EC_{90} values for methylene blue are lower than those obtained for hydroxychloroquine (1.5 μM and 3.0 μM) and azithromycin (20.1 μM and 41.9 μM). The ratios C_{max}/EC_{50} and C_{max}/EC_{90} in blood for methylene blue were estimated at 10.1 and 4.0, respectively, following oral administration and 33.3 and 13.3 following intravenous administration. Methylene blue EC_{50} and EC_{90} values are consistent with concentrations observed in human blood. We propose that methylene blue is a promising drug for treatment of COVID-19. In vivo evaluation in animal experimental models is now required to confirm its antiviral effects on SARS-CoV-2. The potential interest of methylene blue to treat COVID-19 needs to be confirmed by prospective comparative clinical studies.
【저자키워드】 COVID-19, SARS-CoV-2, coronavirus, Antiviral, in vitro, Methylene blue,