*2.11. Molecular Docking*

The protein structure of hemagglutinin (PDB ID: 6CFG) was used for the docking study. All calculations were performed using Discovery Studio 2017. The 3D structures of OA-10 were constructed using the Discovery Studio small molecule window, and energy was minimized by CHARMm force field in a two-step method: steepest descent with RMS gradient convergent to 0.1, and the final step was conjugate gradient with RMS gradient convergent to 0.0001. Prior to the docking procedure, all bound water molecules were removed from the protein crystal structure. A site sphere radius was set to 13.39 Å in which the other parameters were set as default. The docking program CDOCKER was used to perform the automated molecular simulation in which the top hits were set as 10, and the random conformations were set as 20. The top compounds were ranked by the corresponding values of -CDOCKER interaction energy.

#### *2.12. Statistical Analysis*

All values are expressed as means ± SDs from at least three independent experiments. Statistical significance was determined by Student's *t*-test when only two groups were compared or by one-way analysis of variance (ANOVA) when more than two groups were compared. Statistical analyses were performed using GraphPad Prism 7 (GraphPad Software, San Diego, CA, USA). \* *P* < 0.05, \*\* *P* < 0.01 and \*\*\* *P* < 0.001 were considered to be statistically significant at different levels.

### **3. Results**
