Methylene Blue Inhibits the SARS-CoV-2 Spike-ACE2 Protein

Mito

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Abstract

Due to our interest in the chemical space of organic dyes to identify potential small-molecule inhibitors (SMIs) for protein-protein interactions (PPIs), we initiated a screen of such compounds to assess their inhibitory activity against the interaction between SARS-CoV-2 spike protein and its cognate receptor ACE2, which is the first critical step initiating the viral attachment and entry of this coronavirus responsible for the ongoing COVID-19 pandemic. As part of this, we found that methylene blue, a tricyclic phenothiazine compound approved by the FDA for the treatment of methemoglobinemia and used for other medical applications (including the inactivation of viruses in blood products prior to transfusion when activated by light), inhibits this interaction. We confirmed that it does so in a concentration-dependent manner with a low micromolar half-maximal inhibitory concentration (IC50 = 3 μM) in our protein-based ELISA-type setup, while chloroquine, siramesine, and suramin showed no inhibitory activity in this assay. Erythrosine B, which we have shown before to be a promiscuous SMI of PPIs, also inhibited this interaction. Methylene blue inhibited the entry of a SARS-CoV-2 spike bearing pseudovirus into ACE2-expressing cells with similar IC50 (3.5 μM). Hence, this PPI inhibitory activity could contribute to its antiviral activity against SARS-CoV-2 even in the absence of light by blocking its attachment to ACE2-expressing cells and making this inexpensive and widely available drug potentially useful in the prevention and treatment of COVID-19 as an oral or inhaled medication.
 

Jam

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Excellent! An IC50 of 3 μM should equate to a daily dosage of 5-10mg for the average adult.

0.003 mol/L (concentration) * 7L (blood volume in the average adult) * 320 g/mol (molecular weight of methylene blue) = 6.72mg
 

rei

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When a cell has sufficient energy it is less prone to take in adaptation commands in the form of viruses. Serotonin is probably one of the primary mechanisms a cell uses to sense the need to adapt to the environment. This is why serotonin has in several studies shown to be necessary for viral "infection". But i believe both serotonin exposure and energy depletion are needed. Methylene blue fixes the energy depletion, even if it is serotonergic in higher doses.
 

LeeLemonoil

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When a cell has sufficient energy it is less prone to take in adaptation commands in the form of viruses. Serotonin is probably one of the primary mechanisms a cell uses to sense the need to adapt to the environment. This is why serotonin has in several studies shown to be necessary for viral "infection". But i believe both serotonin exposure and energy depletion are needed. Methylene blue fixes the energy depletion, even if it is serotonergic in higher doses.

Smart consideration
 

md_a

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Aug 31, 2015
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Emodin blocks the SARS coronavirus spike protein and angiotensin-converting enzyme 2 interaction

Conclusion

By screening 312 herbs, we identified three widely used Chinese medicinal herbs of the family Polygonaceae which inhibited the SARS-CoV S protein and ACE2 interaction. Emodin, the major components of the genus Rheum and Polygonum, is the likely active constituent responsible for blocking both the binding of SARS-CoV S protein to ACE2 and the infectivity of S protein-pseudotyped retrovirus to Vero E6 cells. These findings suggested that emodin was a novel anti-SARS-CoV compound and might be considered as a potential therapeutic agent in the treatment of SARS.

 

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