CTSL and COVID-19: Only three observational clinical case reports with small numbers of patients (n ≤ 15 for all) speculated that amantadine may be used for COVID-19 treatment, no systematic clinical trial in a human population was performed.47–49 Some other papers only raised a hypothesis but without any validation experiment.50,51 In this study, we systematically investigated the role of amantadine in the treatment of COVID-19 and found that amantadine inhibited CTSL enzyme activity in the setting of SARS-CoV-2 pseudovirus infection.