Methylene Blue Inhibits the SARS-CoV-2 Spike–ACE2 Protein-Protein Interaction–a Mechanism that can Contribute to its Antiviral Activity Against COVID-19

Due to our interest in the chemical space of organic dyes identify potential small-molecule inhibitors (SMIs) for protein-protein interactions (PPIs), we initiated a screen such compounds assess their inhibitory activity against interaction between SARS-CoV-2 spike protein and its cognate receptor ACE2, which is first critical step initiating viral attachment entry this coronavirus responsible ongoing COVID-19 pandemic. As part this, found that methylene blue, tricyclic phenothiazine compound approved by FDA treatment methemoglobinemia used other medical applications (including inactivation viruses blood products prior transfusion when activated light), inhibits interaction. We confirmed it does so concentration-dependent manner with low micromolar half-maximal concentration (IC 50 = 3 ?M) protein-based ELISA-type setup, while chloroquine, siramesine, suramin showed no assay. Erythrosine B, have shown before be promiscuous SMI PPIs, also inhibited Methylene blue bearing pseudovirus into ACE2-expressing cells similar IC (3.5 ?M). Hence, PPI could contribute antiviral even absence light blocking making inexpensive widely available drug potentially useful prevention as an oral or inhaled medication.