SARS-CoV-2 main protease (3CL^pro) interaction with acyclovir antiviral drug/methyl-β-cyclodextrin complex: Physiochemical characterization and molecular docking

During the current outbreak of the novel coronavirus disease 2019 (COVID-19), researchers have examined several antiviral drugs with the potential to inhibit the proliferation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The antiviral drug acyclovir (AVR), which is used to treat COVID-19, in complex with methyl-β-cyclodextrin (Mβ-CD) was examined in the solution and solid phases. UV–visible and fluorescence spectroscopic analyses confirmed that the guest (AVR) was included inside the host (Mβ-CD) cavity. A solid inclusion complex of AVR was prepared by co-precipitation, physical mixing, kneading, and bath sonication methods at a 1:1 ratio of Mβ-CD:AVR. The prepared Mβ-CD:AVR inclusion complex was characterized using Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM) analysis. Phase solubility studies indicated the Mβ-CD:AVR inclusion complex exhibited a higher stability constant and linear enhancement in AVR solubility with increasing Mβ-CD concentrations. In silico analysis of the Mβ-CD/AVR inclusion complex confirmed that AVR drugs show potential as inhibitors of SARS-CoV-2 3C-like protease (3CL^pro) receptors. Results obtained using the PatchDock and FireDock servers indicated that the most favorable docking ligand was Mβ-CD:AVR, which interacted with SARS-CoV-2 (3CL^Pro) protease inhibitors with high geometric shape complementarity scores (2522 and 5872) and atomic contact energy (-313.77 and −214.70 kcal mol⁻¹). Our results suggest that the Mβ-CD/AVR inclusion complex inhibits the main protease of SARS-CoV-2, although further wet-lab experiments are needed to verify these findings.