ABSTRACT
Corona virus pandemic outbreak also known as COVID-19 has created an imbalance in this world. Scientists have adopted the use of natural or alternative medicines which are consumed mostly as dietary supplements to boost the immune system as herbal remedies. India is famous for traditional medicinal formulations which includes 'Trikadu'-a combination of three acrids, namely Zingiber officinale, Piper nigrum and Piper longum which have antioxidant properties that boost our immune system hence acting as a strong preventive measure. In this study, AutoDock 4.0 was used to study interaction between the phytocompounds of Trikadu with RNA-dependent polymerase protein and enveloped protein of the SARS-CoV-2 virus. Analysis of the results showed that coumarin, coumaperine and bisdemethoxycurcumin showed strong bonding interactions with both the proteins. We can conclude that Trikadu has the potential molecules; hence, it can be incorporated in the diet to boost the immune system as a preventive measure against the virus.
Subject(s)
COVID-19 Drug Treatment , COVID-19/immunology , Phytotherapy , Plant Preparations/therapeutic use , SARS-CoV-2 , Antioxidants/isolation & purification , Antioxidants/therapeutic use , COVID-19/virology , Computer Simulation , Coronavirus RNA-Dependent RNA Polymerase/chemistry , Coronavirus RNA-Dependent RNA Polymerase/drug effects , Dietary Supplements , Ginger/chemistry , Humans , Immune System/drug effects , India , Ligands , Medicine, Traditional , Molecular Docking Simulation , Phytochemicals/chemistry , Phytochemicals/therapeutic use , Piper/chemistry , Piper nigrum/chemistry , Plant Preparations/isolation & purification , Plants, Medicinal/chemistry , SARS-CoV-2/chemistry , SARS-CoV-2/drug effects , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/drug effectsABSTRACT
This study aims to identify and isolate the secondary metabolites of Zingiber officinale using GC-MS, preparative TLC, and LC-MS/MS methods, to evaluate the inhibitory potency on SARS-CoV-2 3 chymotrypsin-like protease enzyme, as well as to study the molecular interaction and stability by using docking and molecular dynamics simulations. GC-MS analysis suggested for the isolation of terpenoids compounds as major compounds on methanol extract of pseudostems and rhizomes. Isolation and LC-MS/MS analysis identified 5-hydro-7, 8, 2'-trimethoxyflavanone (9), (E)-hexadecyl-ferulate (1), isocyperol (2), N-isobutyl-(2E,4E)-octadecadienamide (3), and nootkatone (4) from the rhizome extract, as well as from the leaves extract with the absence of 9. Three known steroid compounds, i.e., spinasterone (7), spinasterol (8), and 24-methylcholesta-7-en-3ß-on (6), were further identified from the pseudostem extract. Molecular docking showed that steroids compounds 7, 8, and 6 have lower predictive binding energies (MMGBSA) than other metabolites with binding energy of -87.91, -78.11, and -68.80 kcal/mole, respectively. Further characterization on the single isolated compound by NMR showed that 6 was identified and possessed 75% inhibitory activity on SARS-CoV-2 3CL protease enzyme that was slightly different with the positive control GC376 (77%). MD simulations showed the complex stability with compound 6 during 100 ns simulation time.
Subject(s)
COVID-19 Drug Treatment , Coronavirus 3C Proteases/antagonists & inhibitors , Coronavirus Protease Inhibitors/pharmacology , Ginger/chemistry , Plant Extracts/pharmacology , Coronavirus 3C Proteases/metabolism , Coronavirus 3C Proteases/ultrastructure , Coronavirus Protease Inhibitors/chemistry , Coronavirus Protease Inhibitors/isolation & purification , Coronavirus Protease Inhibitors/therapeutic use , Crystallography, X-Ray , Enzyme Assays , Gas Chromatography-Mass Spectrometry , Humans , Magnetic Resonance Spectroscopy , Molecular Docking Simulation , Molecular Dynamics Simulation , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Extracts/therapeutic use , Pyrrolidines/pharmacology , SARS-CoV-2/drug effects , SARS-CoV-2/enzymology , Structure-Activity Relationship , Sulfonic Acids/pharmacologyABSTRACT
BACKGROUND: The current COVID-19 pandemic is caused by SARS-CoV-2 which belongs to coronaviridae family. Despite the global prevalence, there are currently no vaccines or drugs. Dietary plant derived exosome-like vesicles are known as edible nanoparticles (ENPs). ENPs are filled with microRNAs (miRNAs), in bioavailable form. Recently, cross-kingdom regulation of human transcripts by plant miRNAs have been demonstrated. However, ENP derived miRNAs targeting SARS-CoV-2 has not been described. STUDY DESIGN: Mature ENP-derived miRNA sequences were retrieved from small RNA sequencing datasets available in the literature. In silico target prediction was performed to identify miRNAs that could target SARS-CoV-2. ENPs were isolated from ginger and grapefruit plants and the expression of SARS-CoV-2 targeting miRNAs were confirmed by qRT-PCR. RESULTS: From a total of 260 ENP-derived miRNAs, we identified 22 miRNAs that could potentially target SARS-CoV-2 genome. 11 miRNAs showed absolute target specificity towards SARS-CoV-2 but not SARS-CoV. ENPs from soybean, ginger, hamimelon, grapefruit, tomato and pear possess multiple miRNAs targeting different regions within SARS-CoV-2. Interestingly, osa/cme miR-530b-5p specifically targeted the ribosomal slippage site between ORF1a and ORF1b. We validated the relative expression of six miRNAs (miR-5077, miR-6300, miR-156a, miR-169, miR-5059 and miR-166 m) in ginger and grapefruit ENPs by RT-PCR which showed differential enrichment of specific miRNAs in ginger and grapefruit ENPs. CONCLUSION: Since administration of ENPs leads to their accumulation into lung tissues in vivo, ENP derived miRNAs targeting SARS-CoV-2 genome has the potential to be developed as an alternative therapy.