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

Abstract To discover new drugs to combat COVID-19, an understanding of the molecular basis SARS-CoV-2 infection is urgently needed. Here, for first time, we report crucial role cathepsin L (CTSL) in patients with COVID-19. The circulating level CTSL was elevated after and positively correlated disease course severity. Correspondingly, pseudovirus increased expression human cells vitro ACE2 transgenic mice vivo, while overexpression, turn, enhanced cells. functionally cleaved spike protein virus entry, as evidenced by overexpression knockdown application inhibitor vivo. Furthermore, amantadine, a licensed anti-influenza drug, significantly inhibited activity prevented both Therefore, promising target anti-COVID-19 drug development.