In-vitro and in-silico evaluation of rue herb for SARS-CoV-2 treatment

<p dir="ltr">SARS-CoV-2, a β-coronavirus responsible for the COVID-19 pandemic, has resulted in approximately 4.9 million fatalities worldwide. Despite the urgent need, there is currently no specific therapeutic developed for treating or preventing SARS-CoV-2 infections. The virus en...

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محفوظ في:
التفاصيل البيبلوغرافية
المؤلف الرئيسي: Maliha Khandoker Minu (22224733) (author)
مؤلفون آخرون: Md Enamul Kabir Talukder (22224736) (author), Ramzi A. Mothana (9282050) (author), Sk Injamamul Islam (22224739) (author), Abdullah R. Alanzi (17626502) (author), Sidgi Hasson (22224742) (author), Md Irfan Sadique (22224745) (author), Mohammed Arfat Raihan Chowdhury (19325962) (author), Md Shajid Khan (22224748) (author), Foysal Ahammad (9286524) (author), Farhan Mohammad (256409) (author)
منشور في: 2024
الموضوعات:
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author Maliha Khandoker Minu (22224733)
author2 Md Enamul Kabir Talukder (22224736)
Ramzi A. Mothana (9282050)
Sk Injamamul Islam (22224739)
Abdullah R. Alanzi (17626502)
Sidgi Hasson (22224742)
Md Irfan Sadique (22224745)
Mohammed Arfat Raihan Chowdhury (19325962)
Md Shajid Khan (22224748)
Foysal Ahammad (9286524)
Farhan Mohammad (256409)
author2_role author
author
author
author
author
author
author
author
author
author
author_facet Maliha Khandoker Minu (22224733)
Md Enamul Kabir Talukder (22224736)
Ramzi A. Mothana (9282050)
Sk Injamamul Islam (22224739)
Abdullah R. Alanzi (17626502)
Sidgi Hasson (22224742)
Md Irfan Sadique (22224745)
Mohammed Arfat Raihan Chowdhury (19325962)
Md Shajid Khan (22224748)
Foysal Ahammad (9286524)
Farhan Mohammad (256409)
author_role author
dc.creator.none.fl_str_mv Maliha Khandoker Minu (22224733)
Md Enamul Kabir Talukder (22224736)
Ramzi A. Mothana (9282050)
Sk Injamamul Islam (22224739)
Abdullah R. Alanzi (17626502)
Sidgi Hasson (22224742)
Md Irfan Sadique (22224745)
Mohammed Arfat Raihan Chowdhury (19325962)
Md Shajid Khan (22224748)
Foysal Ahammad (9286524)
Farhan Mohammad (256409)
dc.date.none.fl_str_mv 2024-10-10T12:00:00Z
dc.identifier.none.fl_str_mv 10.1016/j.intimp.2024.113318
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/In-vitro_and_in-silico_evaluation_of_rue_herb_for_SARS-CoV-2_treatment/30094624
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biological sciences
Microbiology
Biomedical and clinical sciences
Pharmacology and pharmaceutical sciences
SARS-CoV-2
Rue herb
Molecular docking
MD simulation
MM-GBSA
PCA
Pharmacophore modeling
Virtual screening
Spike glycoprotein
ADMET
ACE2
dc.title.none.fl_str_mv In-vitro and in-silico evaluation of rue herb for SARS-CoV-2 treatment
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <p dir="ltr">SARS-CoV-2, a β-coronavirus responsible for the COVID-19 pandemic, has resulted in approximately 4.9 million fatalities worldwide. Despite the urgent need, there is currently no specific therapeutic developed for treating or preventing SARS-CoV-2 infections. The virus enters the host by engaging in a molecular interaction between the viral Spike glycoprotein (S protein) and the host ACE2 receptor, facilitating membrane fusion and initiating infection. Inhibiting this interaction could impede viral activity. Therefore, this study aimed to identify natural small molecules from perennial rue herb (<i>Ruta graveolens</i>) as potential inhibitors against the S protein, thus preventing virus infection. Initially, a screening process was conducted on 53 compounds identified from rue herbs, utilizing pharmacophore-based virtual screening approaches. This analysis resulted in the identification of 12 hit compounds. Four compounds, namely Amentoflavone (CID: 5281600), Agathisflavone (CID: 5281599), Vitamin P (CID: 24832108), and Daphnoretin (CID: 5281406), emerged as potential S protein inhibitors through molecular docking simulations, exhibiting binding energies in kcal/mol of −9.2, −8.8, −8.2, and −8.0, respectively. ADMET analysis revealed favorable pharmacokinetics and toxicity profiles for these compounds. The compounds’ stability with respect to the target S protein was evaluated using MD simulation and MM-GBSA approaches. The analysis revealed the stability of the selected compounds with the target protein. Also, PCA revealed distinctive movement patterns in four selected compounds, offered valuable insights into their functional behaviors and potential interactions. In-vitro assays revealed that rue herb extracts containing these compounds displayed potential inhibitory properties against the virus, with an IC50 value of 1.299 mg/mL and a cytotoxic concentration (CC<sub>50</sub>) value of 11.991 mg/mL. The compounds derived from rue herb, specifically Amentoflavone, Agathisflavone, Vitamin P, and Daphnoretin, show promise as candidates for the therapeutic intervention of SARS-CoV-2-related complications.</p><h2>Other Information</h2><p dir="ltr">Published in: International Immunopharmacology<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.intimp.2024.113318" target="_blank">https://dx.doi.org/10.1016/j.intimp.2024.113318</a></p>
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network_acronym_str Manara2
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oai_identifier_str oai:figshare.com:article/30094624
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spelling In-vitro and in-silico evaluation of rue herb for SARS-CoV-2 treatmentMaliha Khandoker Minu (22224733)Md Enamul Kabir Talukder (22224736)Ramzi A. Mothana (9282050)Sk Injamamul Islam (22224739)Abdullah R. Alanzi (17626502)Sidgi Hasson (22224742)Md Irfan Sadique (22224745)Mohammed Arfat Raihan Chowdhury (19325962)Md Shajid Khan (22224748)Foysal Ahammad (9286524)Farhan Mohammad (256409)Biological sciencesMicrobiologyBiomedical and clinical sciencesPharmacology and pharmaceutical sciencesSARS-CoV-2Rue herbMolecular dockingMD simulationMM-GBSAPCAPharmacophore modelingVirtual screeningSpike glycoproteinADMETACE2<p dir="ltr">SARS-CoV-2, a β-coronavirus responsible for the COVID-19 pandemic, has resulted in approximately 4.9 million fatalities worldwide. Despite the urgent need, there is currently no specific therapeutic developed for treating or preventing SARS-CoV-2 infections. The virus enters the host by engaging in a molecular interaction between the viral Spike glycoprotein (S protein) and the host ACE2 receptor, facilitating membrane fusion and initiating infection. Inhibiting this interaction could impede viral activity. Therefore, this study aimed to identify natural small molecules from perennial rue herb (<i>Ruta graveolens</i>) as potential inhibitors against the S protein, thus preventing virus infection. Initially, a screening process was conducted on 53 compounds identified from rue herbs, utilizing pharmacophore-based virtual screening approaches. This analysis resulted in the identification of 12 hit compounds. Four compounds, namely Amentoflavone (CID: 5281600), Agathisflavone (CID: 5281599), Vitamin P (CID: 24832108), and Daphnoretin (CID: 5281406), emerged as potential S protein inhibitors through molecular docking simulations, exhibiting binding energies in kcal/mol of −9.2, −8.8, −8.2, and −8.0, respectively. ADMET analysis revealed favorable pharmacokinetics and toxicity profiles for these compounds. The compounds’ stability with respect to the target S protein was evaluated using MD simulation and MM-GBSA approaches. The analysis revealed the stability of the selected compounds with the target protein. Also, PCA revealed distinctive movement patterns in four selected compounds, offered valuable insights into their functional behaviors and potential interactions. In-vitro assays revealed that rue herb extracts containing these compounds displayed potential inhibitory properties against the virus, with an IC50 value of 1.299 mg/mL and a cytotoxic concentration (CC<sub>50</sub>) value of 11.991 mg/mL. The compounds derived from rue herb, specifically Amentoflavone, Agathisflavone, Vitamin P, and Daphnoretin, show promise as candidates for the therapeutic intervention of SARS-CoV-2-related complications.</p><h2>Other Information</h2><p dir="ltr">Published in: International Immunopharmacology<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.intimp.2024.113318" target="_blank">https://dx.doi.org/10.1016/j.intimp.2024.113318</a></p>2024-10-10T12:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1016/j.intimp.2024.113318https://figshare.com/articles/journal_contribution/In-vitro_and_in-silico_evaluation_of_rue_herb_for_SARS-CoV-2_treatment/30094624CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/300946242024-10-10T12:00:00Z
spellingShingle In-vitro and in-silico evaluation of rue herb for SARS-CoV-2 treatment
Maliha Khandoker Minu (22224733)
Biological sciences
Microbiology
Biomedical and clinical sciences
Pharmacology and pharmaceutical sciences
SARS-CoV-2
Rue herb
Molecular docking
MD simulation
MM-GBSA
PCA
Pharmacophore modeling
Virtual screening
Spike glycoprotein
ADMET
ACE2
status_str publishedVersion
title In-vitro and in-silico evaluation of rue herb for SARS-CoV-2 treatment
title_full In-vitro and in-silico evaluation of rue herb for SARS-CoV-2 treatment
title_fullStr In-vitro and in-silico evaluation of rue herb for SARS-CoV-2 treatment
title_full_unstemmed In-vitro and in-silico evaluation of rue herb for SARS-CoV-2 treatment
title_short In-vitro and in-silico evaluation of rue herb for SARS-CoV-2 treatment
title_sort In-vitro and in-silico evaluation of rue herb for SARS-CoV-2 treatment
topic Biological sciences
Microbiology
Biomedical and clinical sciences
Pharmacology and pharmaceutical sciences
SARS-CoV-2
Rue herb
Molecular docking
MD simulation
MM-GBSA
PCA
Pharmacophore modeling
Virtual screening
Spike glycoprotein
ADMET
ACE2