After one year of the COVID-19 pandemic and hundreds of suggested drugs, will cathepsin L inhibitors be the solution?

Cysteine cathepsins are defined as lysosomal enzymes that members of the papain family. (Cts) prevalently exist in whole organisms, varying from prokaryotes to mammals, and possess greatly conserved cysteine residues their active sites. Cts engaged digestion cellular proteins, activation zymogens, remodeling extracellular matrix (ECM). Host cells entered by SARS-CoV-2 via endocytosis. Cathepsin L phosphatidylinositol 3-phosphate 5-kinase crucial endocytosis cleaving spike protein, which permits viral membrane fusion with endosomal succeeds release genome host cell. Therefore, inhibition cathepsin may be advantageous terms decreasing infection caused SARS-CoV-2. Coordinate multiple function different drugs biological agents might value for some purposes, such a parasite or infections antineoplastic applications. Zn2+ deficiency dysregulation leads exaggerated activity, increasing autoimmune/inflammatory response. For this purpose, metal can safely combined drug increases anti-proteolytic effect endogenous Zn2+, lowering excessive activity CysCts. Biguanide derivative complexes have been found promising inhibitors CysCts protease reactions. Molecular docking studies inhibited metformin-Zn+2 complex performed, showing two strong key interactions (Cys-25&His-163) an extra H-bond Asp-163 compared cocrystallized Zn+2 (PDB ID 4axl).