Fig. 1
From: High-throughput screening and evaluation of repurposed drugs targeting the SARS-CoV-2 main protease
Screening and evaluation of repurposed drugs targeting SARS-CoV-2 Mpro. a SPR plots of the six small molecules binding to Mpro. The real-time binding kinetic profiles of each molecule at a gradient of concentrations were recorded in the sensorgrams with a Biacore system and then the fit curves were constructed by using the steady-state affinity model. These experiments were repeated twice. b Molecular docking poses of the screened candidate drugs in the substrate-binding pocket of Mpro. The relevant parameters of each molecule are listed below each image. c Comparison of the inhibitory efficacies of the identified drugs on the enzymatic activity of Mpro. In a total volume of 280 μL, each reaction component was added triplicate wells with the following final concentrations: 20 μM drug, 1.5 µM Mpro and 10 μM substrate (Dabcyl-KTSAVLQ/SGFRKME-Edans). RFU values were measured every 10 mins with excitation at 340 nm and emission at 510 nm for 3 ~ 6 h. The inhibition rate was calculated based on the change in the average RFU value between each drug treatment and the DMSO control. Results are shown as the means ± SD after two consistently performed independent assays. d Antiviral activity of entrectinib and GC376. Vero E6 cells were infected with SARS-CoV-2 at an MOI of 0.01 for 2 h and then treated with different concentrations of entrectinib or GC376. Forty-eight hours after infection, the supernatants were collected and viral copies were detected by qRT–PCR. Data are shown as the means ± SEM with n = 3 biological replicates. A cutoff line of EC50 is drawn at half of maximum effect by using a dashed line in red. These experiments were repeated twice.
