Cathepsin L plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development

Cathepsin L is a member of the lysosomal protease, whose function is proteolysis of antigens produced by pathogen endocytosis. Circulating cathepsin L level was found to be increased in the plasma of COVID-19 patients. By using an ifection model of VSV pseudovirus possessing SARS-CoV-2 spike protein, the cathepsin L expression was increased by the infection, which was confirmed in human cells and hACE2 transgenic mice. Cathepsin L cleaves the SARS-CoV-2 spike protein and enhances virus entry. The cathepsin L inhibitor efficiently prevents the infection of SARS-CoV-2 spike expressing pseudovirus in cells and animals.