Covid will not pass

The new drug blocks the penetration of SARS-CoV-2 into cells

Svetlana Maslova, Hi-tech+

A new antiviral compound MM3122 was presented by scientists from Washington University in St. Louis. The drug is aimed at capturing the human protein that SARS-CoV-2 needs to enter the cell. 

Article by Mahoney et al. A novel class of TMPRSS2 inhibitors potentially block SARS-CoV-2 and MERS-CoV viral entry and protect human epithelial lung cells is published in the journal Proceedings of the National Academy of Sciences – VM.

The developers said that the drug is promising for the fight against SARS-CoV-2 and other coronaviruses. In preclinical experiments, the effectiveness was significantly higher than remdesivir, while the drug did not show any side effects even with its long-term use in large dosages. With early administration, the drug can prevent severe forms of the disease.

TMPRSS2 protein is a transmembrane serial protease 2. Experiments have shown that the experimental compound effectively blocks TMPRSS2 and another related protein, matriptase, present on the surface of the lungs and other cell types. SARS-CoV-2 and other coronaviruses depend on these proteins and cannot penetrate cells and spread through the respiratory tract to the lungs without them. MM3122 blocks the enzymatic activity of TMPRSS2, which as a result disrupts the work of the spike protein and suppresses infection.

In the figure, MM3122 (yellow) blocks the active site of the human TMPRSS2 protein, which the virus captures in order to enter the VM cells.

MM3122 showed better protection against infection with SARS-CoV-2 in comparison with remdesivir, an antiviral agent that was the first to receive approval from the American regulator FD for use in patients with COVID—19 last year. Scientists have not recorded any side effects in mice after taking the drug for a week in large doses.

MM3122 was equally effective against SARS-CoV-2 and MERS-CoV.

Currently, most inhibitors are aimed at blocking the replication of the virus. Meanwhile, MM3122 is aimed at the earliest stage — preventing infection of cells. With early administration, the drug can prevent severe forms of the disease and complications, the authors said. Now they plan to adapt MM3122 for oral and intranasal administration.

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