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

ABSTRACT

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 (Mpro ). 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 Mpro , 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 Mpro in vitro in a dose-dependent manner. The docking study into SARS-CoV-2 Mpro 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 Mpro .