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.

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Meta-analysis of prospective trials did not detect any significant differences in clinical results, as evidenced by the objective IKDC score, return to preinjury activity level, KT-1000, Lachman test, pivot shift test, extension loss, flexion loss and graft failure. However, the meta-analysis revealed that ACL reconstruction with BPTB autografts resulted in increased anterior knee pain and kneeling pain compared with hamstring autografts. Increased incidence of OA was found after ACL reconstruction at a minimum of 5 years in BPTB group compared with HT autografts. This result should be cautiously interpreted. More high-quality RCT with strictly specified inclusion criteria are highly required before drawing a reliable conclusion.