Interaction of Bioactive Compounds of Moringa oleifera Leaves with SARS-CoV-2 Proteins to Combat COVID-19 Pathogenesis: a Phytochemical and In Silico Analysis

Abstract

Novel SARS-CoV-2 claimed a large number of human lives. The main proteins for viral entry into host cells are SARS-CoV-2 spike glycoprotein (PDB ID: 6VYB) and spike receptor-binding domain bound with ACE2 (spike RBD-ACE2; PDB ID: 6M0J). Currently, specific therapies are lacking globally. This study was designed to investigate the bioactive components from Moringa oleifera leaf (MOL) extract by gas chromatographymass spectroscopy (GC-MS) and their binding interactions with spike glycoprotein and spike RBD-ACE2 protein through computational analysis. GC-MS-based analysis unveiled the presence of thirty-seven bioactive components in MOL extract, viz. polyphenols, fatty acids, terpenes/triterpenes, phytosterols/steroids, and aliphatic hydrocarbons. These bioactive phytoconstituents showed potential binding with SARS-CoV-2 spike glycoprotein and spike RBD-ACE2 protein through the AutoDock 4.2 tool. Further by using AutoDock 4.2 and AutoDock Vina, the top sixteen hits (binding energy ≥ − 6.0 kcal/mol) were selected, and these might be considered as active biomolecules. Moreover, molecular dynamics simulation was determined by the Desmond module. Interestingly two biomolecules, namely β-tocopherol with spike glycoprotein and β-sitosterol with spike RBD-ACE2, displayed the best interacting complexes and low deviations during 100-ns simulation, implying their strong stability and compactness. Remarkably, both β-tocopherol and β-sitosterol also showed the drug-likeness with no predicted toxicity. In conclusion, these findings suggested that both compounds β-tocopherol and β-sitosterol may be developed as anti-SARS-CoV-2 drugs. The current findings of in silico approach need to be optimized using in vitro and clinical studies to prove the effectiveness of phytomolecules against SARS-CoV-2.

In Silico ADME/Tox Profiling of Mushroom Secondary Metabolites

“…The compounds that follow the Brenk criteria and are lead‐like are better candidates for developing medicines since they are far more likely to have advantageous medicinal properties [65] . The in‐silico analysis provides useful information for identifying mushroom‘s secondary metabolites that could be significant for drug discovery altogether [66] . Therefore Kaempferol ( C7 ) and Craterellins C ( C11 ) are the best compounds because they follow the Brenk and Leadlikeness criteria.…”

“…[65] The in-silico analysis provides useful information for identifying mushroom's secondary metabolites that could be significant for drug discovery altogether. [66] Therefore Kaempferol (C7) and Craterellins C (C11) are the best compounds because they follow the Brenk and Leadlikeness criteria.…”

In Silico Approach for the Evaluation of the Potential Antiviral Activity of Extra Virgin Olive Oil (EVOO) Bioactive Constituents Oleuropein and Oleocanthal on Spike Therapeutic Drug Target of SARS-CoV-2

“…Several potential therapeutic approaches have been experimented to treat SARS-CoV-2 infection, such as protein-based vaccine design, the blocking of the angiotensin-converting enzyme 2 (ACE2) receptor, and the effect of phytochemicals on spike protein binding with its ACE2 receptor. Bioactive phytochemicals’ antiviral activity on SARS-CoV-2 was investigated with the aid of molecular docking [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. Furthermore, a combined approach of virtual drug screening, molecular docking, and supervised machine learning techniques were employed in order to identify candidate drugs of chemical libraries with natural products with potential antiviral activity on SARS-CoV-2 [ 30 ].…”