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

doi:10.1016/j.molliq.2022.120292

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

J Mol Liq. 2022 Nov 15:366:120292. doi: 10.1016/j.molliq.2022.120292. Epub 2022 Sep 9.

Affiliations

¹ School of Chemical Engineering, Yeungnam University, Gyeongsan 38541, Republic of Korea.
² Department of Environmental Engineering and Management, Chaoyang University of Technology, Taichung 41349, Taiwan.
³ Department of Physics, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia.
⁴ Department of Physics, Khalifa University of Science and Technology, Abu Dhabi 127788, United Arab Emirates.
⁵ Department of Industrial Chemistry, School of Chemical Sciences, Alagappa University, Karaikudi 630003, Tamilnadu, India.

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 (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.

Keywords: Antiviral drug; COVID-19; In silico; Inclusion complex; Mβ-CD; SARS-CoV-2 (3CLPro) inhibitor.