In vitro inhibition and molecular docking of a new ciprofloxacin‐chalcone against SARS‐CoV‐2 main protease

Alaaeldin, Rania; Mustafa, Muhamad; Abuo‐Rahma, Gamal El‐Din A.; Fathy, Moustafa

BACKGROUND/AIM: SARS‐CoV‐2 is one of the coronavirus families that emerged at the end of 2019. It infected the respiratory system and caused a pandemic worldwide. Fluoroquinolones (FQs) have been safely used as antibacterial agents for decades. The antiviral activity of FQs was observed. Moreover, substitution on the C‐7 position of ciprofloxacin enhanced its antiviral activity. Therefore, this study aims to investigate the antiviral activity of 7‐(4‐(N‐substituted‐carbamoyl‐methyl)piperazin‐1yl)‐chalcone in comparison with ciprofloxacin against SARS‐CoV‐2 main protease (M(pro)). MATERIALS AND METHODS: Vero cells were infected with SARS‐CoV‐2. After treatment with ciprofloxacin and the chalcone at the concentrations of 1.6, 16, 160 nmol/L for 48 h, SARS‐CoV‐2 viral load was detected using real‐time qPCR, SARS‐CoV‐2 infectivity was determined using plaque assay, and the main protease enzyme activity was detected using in vitro 3CL‐protease inhibition assay. The activity of the chalcone was justified through molecular docking within SARS‐CoV‐2 M(pro), in comparison with ciprofloxacin. RESULTS: The new chalcone significantly inhibited viral load replication where the EC50 was 3.93 nmol/L, the plaque formation ability of the virus was inhibited to 86.8% ± 2.47. The chalcone exhibited a significant inhibitory effect against SARS‐CoV‐2 M(pro) in vitro in a dose‐dependent manner. The docking study into SARS‐CoV‐2 M(pro) active site justified the importance of adding a substitution to the parent drug. Additionally, the assessment of the drug‐likeness properties indicated that the chalcone might have acceptable ADMET properties. CONCLUSION: The new chalcone might be useful and has new insights for the inhibition of SARS‐CoV‐2 M(pro).