Journal
MOLECULES
Volume 27, Issue 6, Pages -Publisher
MDPI
DOI: 10.3390/molecules27061793
Keywords
molecular docking; SARS-CoV-2 main protease; coronavirus; quinoline
Funding
- Thailand Science Research and Innovation (TSRI) [2536708/41859]
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In this study, the binding interactions of phenylamino-phenoxy-quinoline derivatives and SARS-CoV-2 main protease (M-pro) were investigated, and two compounds were found to have low binding energy values and appropriate molecular properties for binding to M-pro via hydrogen bonding and Pi-Pi stacking interactions.
In the search for new anti-HIV-1 agents, two forms of phenylamino-phenoxy-quinoline derivatives have been synthesized, namely, 2-phenylamino-4-phenoxy-quinoline and 6-phenylamino-4-phenoxy-quinoline. In this study, the binding interactions of phenylamino-phenoxy-quinoline derivatives and six commercially available drugs (hydroxychloroquine, ritonavir, remdesivir, S-217622, N3, and PF-07321332) with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (M-pro) were investigated using molecular docking and the ONIOM method. The molecular docking showed the hydrogen bonding and hydrophobic interactions of all the compounds in the pocket of SARS-CoV-2 main protease (M-pro), which plays an important role for the division and proliferation of the virus into the cell. The binding free energy values between the ligands and M-pro ranged from -7.06 to -10.61 kcal/mol. The molecular docking and ONIOM results suggested that 4-(2 ',6 '-dimethyl-4 '-cyanophenoxy)-2-(4 ''-cyanophenyl)-aminoquinoline and 4-(4 '-cyanophenoxy)-2-(4 ''-cyanophenyl)-aminoquinoline have low binding energy values and appropriate molecular properties; moreover, both compounds could bind to M-pro via hydrogen bonding and Pi-Pi stacking interactions with amino acid residues, namely, HIS41, GLU166, and GLN192. These amino acids are related to the proteolytic cleavage process of the catalytic triad mechanisms. Therefore, this study provides important information for further studies on synthetic quinoline derivatives as antiviral candidates in the treatment of SARS-CoV-2.
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