Ciprofloxacin and moxifloxacin could interact with SARS-CoV-2 protease: preliminary in silico analysis

Abstract

Background: A large body of research has focused on fluoroquinolones. It was shown that this class of synthetic antibiotics could possess antiviral activity as a broad range of anti-infective activities. Based on these findings, we have undertaken in silico molecular docking study to demonstrate, for the first time, the principle for the potential evidence pointing ciprofloxacin and moxifloxacin ability to interact with COVID-19 Main Protease.

Methods: In silico molecular docking and molecular dynamics techniques were applied to assess the potential for ciprofloxacin and moxifloxacin interaction with COVID-19 Main Protease (M^pro). Chloroquine and nelfinavir were used as positive controls.

Results: We revealed that the tested antibiotics exert strong capacity for binding to COVID-19 Main Protease (M^pro). According to the results obtained from the GOLD docking program, ciprofloxacin and moxifloxacin bind to the protein active site more strongly than the native ligand. When comparing with positive controls, a detailed analysis of the ligand-protein interactions shows that the tested fluoroquinolones exert a greater number of protein interactions than chloroquine and nelfinavir. Moreover, lower binding energy values obtained from K_DEEP program were stated when compared to nelfinavir.

Conclusions: Here, we have demonstrated for the first time that ciprofloxacin and moxifloxacin may interact with COVID-19 Main Protease (M^pro).

Keywords: COVID-19 Main Protease (Mpro); Ciprofloxacin; Molecular docking; Moxifloxacin.

Fig. 1

Structure of compounds used in this study

Fig. 2

Docking pose of COVID-19 M^pro protein complex with HWH (a), ciprofloxacin (b), moxifloxacin (c), chloroquine (d) and nelfinavir (e)

Fig. 3

The visualization of hydrogen bonds (green) and hydrophobic interaction (violet and yellow) between HWH (a in crystal structure and b redocked), ciprofloxacin (c), moxifloxacin (d), chloroquine (e) and nelfinavir (f) with COVID-19 M^pro

Fig. 4

Binding 2D model of HWH (a in crystal structure and b redocked) and predicted binding model of ciprofloxacin (c), moxifloxacin (d), chloroquine (e) and nelfinavir (f) with COVID-19 M^pro

Fig. 5

RMSD values of protein backbones in protein–ligand complexes

Fig. 6

RMSD values of ligands in protein–ligand complexes