Fig. 5

Molecular docking analysis with compounds of coffee and TMPRSS2. a Surface view of Caffeine, CGA, isoCGA-A, isoCGA-B and isoCGA-C docking to TMPRSS2. The surface charge distribution of TMPRSS2 shows the positively (blue) and negatively charged (red) area, respectively. b 3D visualization of hydrogen bonds between Caffeine, CGA, isoCGA-A, isoCGA-B and isoCGA-C with TMPRSS2 amino acids. Three hydrogen bond interactions were formed between Caffeine and TMPRSS2 amino acids Ser441, Gly464 and Cys465. Two hydrogen bond interactions were formed between CGA and TMPRSS2 amino acids Ser441 and Ser436. Five hydrogen bond interactions were formed between isoCGA-A and TMPRSS2 amino acids His296, Gly385, Ser441 and Gly439. Three hydrogen bond interactions were formed between isoCGA-B and TMPRSS2 amino acids His296, Gly385 and Gly439. Three hydrogen bond interactions were formed between isoCGA-C and TMPRSS2 amino acids Gln438, Ser441 and Val473. Hydrogen bonds are shown as black dashed lines. c Validation of the ability of caffeine, CGA, isoCGA-A, isoCGA-B, and isoCGA-C at 0, 25, 50, 100, and 200 μM to repress TMPRSS2 activity using a cell-based TMPRSS2 enzyme activity assay. d Effect of 5 compounds tested by Vpp (MOI = 0.1) on TMPRSS2 involvement in SARS-CoV-2 entry in 293 T-ACE2 and 293 T-ACE2-TMPRSS2 cells. e Through Western blot to test 5 compounds at 100 μM impact cleavage of SARS-CoV-2 S by TMPRSS2. f Huh7 cells were treated with different concentrations of 5 compounds at 0, 6.25, 25, and 100 μM for CTSL activity. Error bars indicated the standard error of the mean in triplicate independent experiments. P values were obtained by the Student T-test. Statistical significance was concerned as *P < 0.05