COVID-19 has broken out since the end of December 2019 and is still spreading rapidly, which has been listed as an international concerning public health emergency. We found the Spike protein of SARS-CoV-2 contains a furin cleavage site, which did not exist in any other betacoronavirus subtype B. Based on a series of analysis, we speculate that the presence of a redundant furin cut site in its Spike protein is responsible for SARS-CoV-2’s stronger infectious than other coronaviruses, which leads to higher membrane fusion efficiency. Subsequently, a library of 4,000 compounds including approved drugs and natural products were screened against furin through structure-based virtual screening and then assayed for their inhibitory effects on furin activity. Among them, an anti-parasitic drug, Diminazene , showed the highest inhibition effects on furin with an IC 50 of 5.42 ± 0.11 μM, which might be used for the treatment of COVID-19.

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