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

During the current outbreak of the novel coronavirus disease 2019 (COVID-19), researchers have exam-ined 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-O-cyclodextrin (MO-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 (MO-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 MO-CD:AVR. The prepared MO-CD:AVR inclusion complex was characterized using Fourier transform infrared spectroscopy (FTIR), X-ray powder diffrac-tion (XRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and scanning elec-tron microscopy (SEM) analysis. Phase solubility studies indicated the MO-CD:AVR inclusion complex exhibited a higher stability constant and linear enhancement in AVR solubility with increasing MO-CD concentrations. In silico analysis of the MO-CD/AVR inclusion complex confirmed that AVR drugs show potential as inhibitors of SARS-CoV-2 3C-like protease (3CLpro) receptors. Results obtained using the PatchDock and FireDock servers indicated that the most favorable docking ligand was MO-CD:AVR, which interacted with SARS-CoV-2 (3CLPro) 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 MO-CD/AVR inclusion complex inhibits the main protease of SARS-CoV-2, although further wet -lab experiments are needed to verify these findings.(c) 2022 Elsevier B.V. All rights reserved.

Automated summary

During the COVID-19 outbreak, researchers examined a complex that includes an antiviral drug and a host molecule, which showed potential to inhibit the main protease of SARS-CoV-2, thus preventing the virus from proliferating.