A Comprehensive Molecular Dynamic Simulation Study of Plant Bioactive Phytoconstituents as Inhibitors for SARS-CoV-2 Main Protease and Spike (S) Glycoprotein.
{"title":"A Comprehensive Molecular Dynamic Simulation Study of Plant Bioactive Phytoconstituents as Inhibitors for SARS-CoV-2 Main Protease and Spike (S) Glycoprotein.","authors":"Vinay Mohan Kandpal, Apoorv Tiwari, Pranabesh Mandal, Durg Vijay Singh, Gohar Taj, Sandhya Upadhyay","doi":"10.2174/0115734099285818240626110217","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Since the commencement of the COVID-19 pandemic, researchers have been earnestly exploring the capacity of diverse bioactive compounds present in plants to impede the transmission of SARS-CoV-2. Plants have always held a special place in scientific research as invaluable bio-factories capable of producing a diverse array of chemical compounds with promising therapeutic applications. Cichorium intybus is among these plants, known for its rich reservoir of bioactive phytoconstituents with significant potential for variable health benefits.</p><p><strong>Objective: </strong>The current work aims to investigate the antiviral activity of various phytoconstituents against SARS-CoV-2 by inhibiting the main protease (Mpro) (PDB code: 6LU7) and spike (S) glycoprotein receptor binding domain (RBD) to Angiotensin-converting enzyme 2 (ACE2) (PDB code: 6M0J) of SARS-CoV-2 and Omicron main protease (PDB code: 7TOB).</p><p><strong>Methods: </strong>Auto Dock Vina was employed as the docking engine for the evaluation and determination of docking scores. To test whether a chemical satisfies the requirements for an active drug taken orally in humans, the rule of five (Ro5) was calculated. By choosing the proteinligand complex geometry having the highest affinities (highest negative Gibbs' free energy of binding/G), the docking score was calculated. The FDA-recommended antimalarial medications chloroquine and hydroxychloroquine sulfate, Remdesivir, and the antiviral medication nelfinavir were utilized as comparisons.</p><p><strong>Results: </strong>The results demonstrate that as spike glycoprotein inhibitors, crepidiaside B, 3,5-Dicaffeoylquinic acid, 4,5 -Dicaffeoylquinic acid, and crepidiside A performed better than nelfinavir, chloroquine, hydroxychloroquine sulfate, and remdesivir. The sequence of chemical reactivity of the chosen bioactive phytoconstituents, as determined by quantum chemical DFT calculations, was Crepidiside A <Crepidiaside B < 4,5-Dicaffeoylquinic acid < 3,5 -Dicaffeoylqu inic acid. The C=O portions of all isolated compounds favor an electrophilic assault, while the O-H sections are ideal for a nucleophilic attack. Additionally, Homo- Lumo values for the chosen compounds showed a noteworthy and satisfactory profile. Furthermore, the molecular dynamics simulation confirmed the stable nature of protein-ligand interaction and highlighted the amino acid residues implicated in binding.</p><p><strong>Conclusion: </strong>The current investigation discovered bioactive phytoconstituents derived from plants that have the potential to be developed as therapeutic alternatives for COVID-19.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current computer-aided drug design","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2174/0115734099285818240626110217","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
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Abstract
Background: Since the commencement of the COVID-19 pandemic, researchers have been earnestly exploring the capacity of diverse bioactive compounds present in plants to impede the transmission of SARS-CoV-2. Plants have always held a special place in scientific research as invaluable bio-factories capable of producing a diverse array of chemical compounds with promising therapeutic applications. Cichorium intybus is among these plants, known for its rich reservoir of bioactive phytoconstituents with significant potential for variable health benefits.
Objective: The current work aims to investigate the antiviral activity of various phytoconstituents against SARS-CoV-2 by inhibiting the main protease (Mpro) (PDB code: 6LU7) and spike (S) glycoprotein receptor binding domain (RBD) to Angiotensin-converting enzyme 2 (ACE2) (PDB code: 6M0J) of SARS-CoV-2 and Omicron main protease (PDB code: 7TOB).
Methods: Auto Dock Vina was employed as the docking engine for the evaluation and determination of docking scores. To test whether a chemical satisfies the requirements for an active drug taken orally in humans, the rule of five (Ro5) was calculated. By choosing the proteinligand complex geometry having the highest affinities (highest negative Gibbs' free energy of binding/G), the docking score was calculated. The FDA-recommended antimalarial medications chloroquine and hydroxychloroquine sulfate, Remdesivir, and the antiviral medication nelfinavir were utilized as comparisons.
Results: The results demonstrate that as spike glycoprotein inhibitors, crepidiaside B, 3,5-Dicaffeoylquinic acid, 4,5 -Dicaffeoylquinic acid, and crepidiside A performed better than nelfinavir, chloroquine, hydroxychloroquine sulfate, and remdesivir. The sequence of chemical reactivity of the chosen bioactive phytoconstituents, as determined by quantum chemical DFT calculations, was Crepidiside A
Conclusion: The current investigation discovered bioactive phytoconstituents derived from plants that have the potential to be developed as therapeutic alternatives for COVID-19.
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