The role of proteases in the invasion of SARS-CoV-2 virus into human host cells

Maryam Saeidi, Fatemeh Rouhollah


The new coronavirus, which originally broke out in Wuhan, China, in December 2019, increase quickly around the world, causing a pandemic all over the world. The virus uses its spike protein to enter the human host cells. Protein S binds to the angiotensin-converting enzyme II (ACE2) receptor and enters the host cell. For the more successful binding, several proteases facilitate and optimize this binding, the most important of which are transmembrane protease serine 2 (TMPRSS2), furin, and cathepsin L proteases. After binding of protein S to the ACE2 receptor, cleavage of protein S is required for membrane fusion by protein S, which causes viral entry into host cells. This proteolytic activity may be cathepsin L-dependent and occurs with changes in pH in cell endosomes, or it may occur through serine proteases activity at the surface of the host cell membrane or within vesicles. Finally, the cell becomes infected with the virus. Several studies have tried to reduce the rate of viral infection by using inhibitors of these proteases.


SARS-CoV-2; TMPRSS2; Furin; Cathepsin L; COVID-19


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