Abstract
Papain-like protease (PL pro ) is a key enzyme encoded by SARS-CoV-2 that is essential for viral replication and immune evasion. Significant suppression of viral spread and promotion of antiviral immunity can be achieved by inhibition of PL pro , revealing an inspiring strategy for COVID-19 treatment. This study aimed to discover PL pro inhibitors by investigating the national compound library of traditional Chinese medicines (NCLTCMs), a phytochemical library comprising over 9000 TCM-derived compounds. Through virtual screening and enzymatic evaluations, nine natural biflavones were confirmed to be effective PL pro inhibitors with IC 50 values ranging from 9.5 to 43.2 μM. Pro-ISG15 cleavage assays further demonstrated that several biflavones exhibited potent inhibitory effects against PL pro -mediated deISGylation, a key process involved in viral immune evasion. Herein, we report the discovery, antiviral evaluation, structure-activity relationship elucidation and molecular docking investigation of biflavones as potent inhibitors of SARS-CoV-2 PL pro .
Keywords: Antiviral; Natural biflavone; Papain-like protease; SARS-CoV-2; deISGylation.
【저자키워드】 SARS-CoV-2, Antiviral, Papain-like protease, Natural biflavone, deISGylation., 【초록키워드】 COVID-19, Treatment, Antiviral, molecular docking, Traditional Chinese medicine, Virtual screening, protease, viral spread, COVID-19 treatment, Papain-like protease, immune evasion, viral replication, Viral immune evasion, cleavage, inhibitor, antiviral immunity, compounds, traditional Chinese medicines, natural, inhibitors of SARS-CoV-2, enzyme, inhibitory effect, Papain, promotion, National, effective, involved, nine, exhibited, in viral, demonstrated, Significant, 【제목키워드】 inhibitor, natural,