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.…”

Potential pharmacokinetic interactions with concurrent use of herbal medicines and a ritonavir-boosted COVID-19 protease inhibitor in low and middle-income countries

“…( Kashyap et al, 2022 ; Liu et al, 2022 ). Previously reported analgesic, anti-inflammatory, antipyretic and immune boosting properties render moringa a potentially viable treatment for the management of COVID-19 ( Chikowe et al, 2021 ; Nuertey et al, 2022 ; Siddiqui et al, 2022 ). However, some preclinical and clinical safety data indicate the potential for HDIs.…”

Herbal concoction Unveiled: A computational analysis of phytochemicals' pharmacokinetic and toxicological profiles using novel approach methodologies (NAMs)

“…The compounds that are Lead-like and adhere to the Brenk rules are superior prospects for drug development because they are more likely to possess favorable pharmacological characteristics ( Andricopulo et al, 2009 ). Overall, the in-silico study offers helpful data for the finding of phytochemicals that may be useful for drug discovery ( Siddiqui et al, 2022 ).…”