Design, DFT, docking and in silico analysis of alkaloids acyl derivatives as potential inhibitors of SARS-CоV-2 main protease M^pro

In the present work, at first, density functional theory calculations were performed to investigate the molecular structure anabasine, cytisine, quinine alkaloids acyl derivatives by CAM-B3LYP/MidiX level of theory. A detail of quantum molecular descriptors of the title compounds such as Ionization Potential (IP) and Electron Affinities (EA), Hardness (η), Softness (S), Electronegativity (μ), Electrophilic Index (ω), Electron Donating Power (ω^–), Electron Accepting Power (ω⁺) and Energy Gap (E_g) have been calculated. Pharmacokinetic properties of the title compounds and their bioactivity were investigated. In the following, a molecular docking study was carried out to screen for effective available compound which may work as a strong inhibitor for the SARS-CoV-2 main protease M^pro. The binding energy between SARS-CoV-2 main protease M^pro and derivatives of natural alkaloids showed a good binding affinity. Therefore, studied derivatives of natural alkaloids can be used for potential application against the SARS-CoV-2 main protease M^pro.

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