Theoretical study on inhibitability of some natural alkaloids against influenza virus hemagglutinin and SARS-CoV-2 main protease

Abstract

Berberine (V1), lycorine (V2), hemanthamine (V3), aloperin (V4), dendrobine (V5) possess structural frameworks resembling known anti-influenza and anti-SARS-CoV-2 drugs, thus subjected for a computational screening. Their quantum properties were examined using density functional theory (DFT); the ligand-protein inhibitability was evaluated using molecular docking simulation; physicochemical properties were obtained from QSARIS-based analysis in reference to Lipinski's rule of five; pharmacokinetic parameters were assessed by ADMET-based analysis. DFT calculations indicate that there are no abnormal bonding constraints observed; NBO analysis suggests all possessing favorable electric configurations for intermolecular inhibition. Regarding ligand-2VIU, the order for static inhibitability is V3-2VIU > V2-2VIU > V1-2VIU > V5-2VIU > V4-2VIU; Regarding ligand-6LU7, the corresponding order follows: V2-6LU7 > V3-6LU7 > V1-6LU7 > V5-6LU7 > V4-6LU7. An exceptional hydrophilic bonding (π-cation) with the associated Gibbs free energy of -10.9 kcal.mol-1 is detected in inhibitory complex V1-2VIU. QSARIS-based analysis reveals that all the candidates are highly bio-compatible. ADMET-based analysis specifies V2 and V3 as being safe and suitable for the use as orally administrated drugs. The results encourage further investigations for more in-depth mechanisms and experimental validations, such as molecular dynamics simulation and in vitro enzyme assays.