Methylene blue inhibits the replication of SARS-Cov-2 in vitro

Gendrot, Mathieu; Andreani, Julien; Duflot, Isabelle; Boxberger, Manon; Bideau, Marion Le; Mosnier, Joel; Jardot, Priscilla; Fonta, Isabelle; Rolland, Clara; Bogreau, Hervé; Hutter, Sébastien; La Scola, Bernard; Pradines, Bruno

In December 2019, a new severe acute respiratory syndrome coronavirus (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 needed. Methylene blue already demonstrated in vitro antiviral activity in photodynamic therapy, and antibacterial, antifungal or antiparasitic activity in nonphotodynamic assays. Non-photoactivated methylene blue showed in vitro activity at very low-micromolar range with EC(50) of 0.3 ± 0.03 µM and EC(90) of 0.75 ± 0.21 µM at MOI of 0.25 against SARS-CoV-2. The EC(50) and EC(90) values for methylene blue are lower than those obtained for hydroxychloroquine (1.5 and 3.0 µM) and azithromycin (20.1 and 41.9 µM). The ratios C(max)/EC(50) and C(max)/EC(90) in blood for methylene blue after oral administration were estimated at 10.1 and 4.0, respectively, and 33.3 and 13.3 after intravenous administration. Methylene blue EC(50) and EC(90) are consistent with concentrations observed in human blood. We propose that methylene blue is a promising drug for COVID-19 treatment. 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.