In silico Evaluation of Anacyclus pyrethrum Composition for Inhibition of Spike RBD-ACE-2 Interaction to Treat COVID-19

Abstract

The spike glycoprotein of SARS-CoV-2, via its S1-subunit, binds with host angiotensin-converting enzyme 2 (ACE-2) receptors, and its S2-subunit mediates the fusion of the virus to the host cell. The entry of SARS-CoV-2 inside the host cell can be prevented by inhibition of the receptor binding domain (RBD) of S1-subunit of the spike. Anacyclus pyrethrum, a native herb of Algeria, Spain and Morocco has antidepressant, analgesic, antimicrobial, anesthetic, antioxidant, anti-inflammatory, aphrodisiac, antidiabetic and immunostimulant effects. Still, its antiviral effect has not been established yet. The present study deals with ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity), molecular docking and molecular dynamic simulation based investigation to evaluate the potential of Anacyclus pyrethrum constituents for effective spike RBD inhibition. ADMET analysis revealed that 10 out of 12 significant constituents belongs to toxicity class 4 to 6 proving least toxicity of the plant extract with high LD50 values. Molecular docking analysis of 10 considered compounds revealed that morphinan-6-one, 4,5.alpha.-epoxy-3-hydroxy-17-methyl, a derivative of morphine (well-known analgesic and anti-inflammatory compound) gave the maximum negative binding energy of -6.9Kcal/mol in best-docked conformation with spike RBD having 2 hydrogen bonds. Molecular dynamic simulation disclosed effective RMSD, RMSF, and Rg values over the simulation trajectory with significant hydrogen bonding proving stable interaction of the compound with that of the spike RBD. Hence, all these outcomes revealed the outstanding potential of the Anacyclus pyrethrum extract to inhibit the spike RBD of SARS-CoV-2. Therefore, further in-vitro investigation can develop natural and effective treatments against COVID-19 disease.