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