人工知能支援活性予測システムによって選択されたクルクミンとその類縁体のSARS-CoV-2感染VeroE6細胞を用いた抗ウイルス活性

抄録

Curcumin has been reported to exert its anti-SARS-CoV-2 activity through multiple mechanisms including inhibition of spike receptor-binding domain (RBD) to angiotensin-converting enzyme-2 (ACE2) binding. To identify more potent compounds, we tested curcumin and its analogs for spike RBD-ACE2 binding inhibitory activity and antiviral activity in SARS-CoV-2-infected cells. An artificial intelligence (AI) -supported activity prediction system was used to select the compounds, and 116 compounds with a docking score range of -8.7 to -4.3 kcal/mol were selected from 334 curcumin analogs. These compounds were narrowed down to 10 compounds, including curcumin, for confirmatory studies. These 10 compounds showed a significant correlation (r_s=0.685, P=0.029) between the IC₂₀ values of spike-RBD-ACE2 binding inhibitory activity and EC₅₀ values of antiviral activity, indicating that the antiviral activity was mediated by spike RBD-ACE2 binding inhibition. Based on the assumption that the binding site of curcumin and its analogs is different from that of anti-spike RBD antibody drugs, it is expected that these compounds through pharmaceutical or pharmacokinetic modification, or the development of more potent derivatives would contribute to supplementing the antiviral activity of antibodies against SARS-CoV-2.