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

Sonaimuthu Mohandoss, Ramaraj Sukanya, Sivarasan Ganesan, Fatemah H. Alkallas, Amira Ben Gouider Trabelsi, Fedor V. Kusmartsev, Kuppu Sakthi Velu, Thambusamy Stalin, Huang Mu Lo, Yong Rok Lee

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8 Scopus citations

Abstract

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 (3CLpro) 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 (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 Mβ-CD/AVR inclusion complex inhibits the main protease of SARS-CoV-2, although further wet-lab experiments are needed to verify these findings.

Original languageBritish English
Article number120292
JournalJournal of Molecular Liquids
Volume366
DOIs
StatePublished - 15 Nov 2022

Keywords

  • Antiviral drug
  • COVID-19
  • In silico
  • Inclusion complex
  • Mβ-CD
  • SARS-CoV-2 (3CL) inhibitor

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