Microvascular injury and thrombosis due to severe COVID-19 infection
Uncontrolled, excessive complement activation can cause severe complications during viral infections. While the complement contributes to the elimination of viruses and infected cells, its overactivation can trigger harmful inflammatory reactions. A primary cause of death of COVID patients is severe respiratory failure. As the complement lectin pathway affects blood coagulation, it can contribute to the development of arterial thrombosis and severe endothelial damage in the lung tissue. The coronavirus proteins have been shown to activate the lectin pathway, especially the MASP-2 protease. In the lung and kidney tissues of COVID-19 patients, heavy MASP-2 deposition has been detected.
Inhibition of MASP-2 could reduce inflammation, endothelial damage, and thrombosis in COVID patients. It would not lead to complete immunosuppression, as the classical and alternative pathways still maintain protection against pathogen microorganisms. EvolVeritas has developed selective and efficient MASP-2 inhibitors by directed protein evolution. These proteins completely abolish MASP-2 proteolytic activity, while they do not inhibit other proteases in the blood, such as enzymes of the blood coagulation or fibrinolysis.
In animal experiments these inhibitors were extremely efficient at shutting down the lectin pathway, while they were non-toxic even at high concentration.