TY - JOUR
T1 - SARS-CoV-2 main protease (3CLpro) interaction with acyclovir antiviral drug/methyl-β-cyclodextrin complex
T2 - Physiochemical characterization and molecular docking
AU - Mohandoss, Sonaimuthu
AU - Sukanya, Ramaraj
AU - Ganesan, Sivarasan
AU - Alkallas, Fatemah H.
AU - Ben Gouider Trabelsi, Amira
AU - Kusmartsev, Fedor V.
AU - Sakthi Velu, Kuppu
AU - Stalin, Thambusamy
AU - Lo, Huang Mu
AU - Rok Lee, Yong
N1 - Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) ( 2021R1A2B5B02002436 and 2021R1F1A1061566 ). This research was funded by Princess Nourah bint Abdulrahman University Researchers Supporting Project number ( PNURSP2022R223 ), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.
Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2022/11/15
Y1 - 2022/11/15
N2 - 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.
AB - 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.
KW - Antiviral drug
KW - COVID-19
KW - In silico
KW - Inclusion complex
KW - Mβ-CD
KW - SARS-CoV-2 (3CL) inhibitor
UR - http://www.scopus.com/inward/record.url?scp=85138045410&partnerID=8YFLogxK
U2 - 10.1016/j.molliq.2022.120292
DO - 10.1016/j.molliq.2022.120292
M3 - Article
AN - SCOPUS:85138045410
SN - 0167-7322
VL - 366
JO - Journal of Molecular Liquids
JF - Journal of Molecular Liquids
M1 - 120292
ER -
