Docking Analysis of Some Bioactive Compounds from Traditional Plants against SARS-CoV-2 Target Proteins

• Published in: Molecules (Basel, Switzerland) Switzerland), 2022-04, Vol.27 (9), p.2662
• Main Authors: Abd El-Aziz, Nourhan M, Khalifa, Ibrahim, Darwish, Amira M G, Badr, Ahmed N, Aljumayi, Huda, Hafez, El-Sayed, Shehata, Mohamed G
• Format: Article
• Language: English
• Subjects: Affinity; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Binding energy; Bioactive compounds; Biological activity; Caffeic acid; Coronaviruses; COVID-19; COVID-19 - drug therapy; Curcumin; Cytochrome P450; Cytochromes P450; Disease; DNA-directed RNA polymerase; Energy; Enzymes; Hepatitis; Herbal medicine; HIV; Human immunodeficiency virus; Humans; Immune system; Infections; Ligands; Medicinal plants; Molecular docking; Molecular Docking Simulation; Multidrug resistance; Papain; Peptide Hydrolases; pharmacokinetic; Pharmacokinetics; Pharmacology; Proteins; Quinine; RNA-Dependent RNA Polymerase; SARS-CoV-2; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Spike protein; Substrates; Thermodynamics; traditional plants; Viral infections; Viruses
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules27092662

COVID-19 is still a global pandemic that has not been stopped. Many traditional medicines have been demonstrated to be incredibly helpful for treating COVID-19 patients while fighting the disease worldwide. We introduced 10 bioactive compounds derived from traditional medicinal plants and assessed their potential for inhibiting viral spike protein (S-protein), Papain-like protease (PLpro), and RNA dependent RNA polymerase (RdRp) using molecular docking protocols where we simulate the inhibitors bound to target proteins in various poses and at different known binding sites using Autodock version 4.0 and Chimera 1.8.1 software. Results found that the chicoric acid, quinine, and withaferin A ligand strongly inhibited CoV-2 S -protein with a binding energy of -8.63, -7.85, and -7.85 kcal/mol, respectively. Our modeling work also suggested that curcumin, quinine, and demothoxycurcumin exhibited high binding affinity toward RdRp with a binding energy of -7.80, -7.80, and -7.64 kcal/mol, respectively. The other ligands, namely chicoric acid, demothoxycurcumin, and curcumin express high binding energy than the other tested ligands docked to PLpro with -7.62, -6.81, and -6.70 kcal/mol, respectively. Prediction of drug-likeness properties revealed that all tested ligands have no violations to Lipinski's Rule of Five except cepharanthine, chicoric acid, and theaflavin. Regarding the pharmacokinetic behavior, all ligand predicted to have high GI-absorption except chicoric acid and theaflavin. At the same way chicoric acid, withaferin A, and withanolide D predicted to be substrate for multidrug resistance protein (P-gp substrate). Caffeic acid, cepharanthine, chicoric acid, withaferin A, and withanolide D also have no inhibitory effect on any cytochrome P450 enzymes. Promisingly, chicoric acid, quinine, curcumin, and demothoxycurcumin exhibited high binding affinity on SARS-CoV-2 target proteins and expressed good drug-likeness and pharmacokinetic properties. Further research is required to investigate the potential uses of these compounds in the treatment of SARS-CoV-2.