Targeting the Complement Serine Protease MASP-2 as a Therapeutic Strategy for Coronavirus Infections

MASP-2, mannose-binding protein-associated serine protease 2, is a key enzyme in the lectin pathway of complement activation. Hyperactivation this protein by human coronaviruses SARS-CoV, MERS-CoV and SARS-CoV-2 has been found to contribute aberrant activation patients, leading aggravated lung injury with potentially fatal consequences. This hyperactivation triggered lungs through conserved, direct interaction between MASP-2 coronavirus nucleocapsid (N) proteins. Blocking monoclonal antibodies interfering directly catalytic activity have alleviate coronavirus-induced both vitro vivo. In study, virtual library 8736 licensed drugs clinical agents screened silico according two parallel strategies. The first strategy aims at identifying inhibitors activity, while second focusses on finding protein-protein (PPIs) coronaviral N Such could represent promising support treatment options prevent reduce mortality rates infections caused present future-emerging coronaviruses. Forty-six drug repurposing candidates were purchased and, for ones selected as potential preliminary assay was conducted assess their interference Some tested displayed dose-response inhibitory pathway, providing basis viable severe complications infections.