<i>Syzygium aromaticum</i> Phytoconstituents Target SARS-CoV-2: Integrating Molecular Docking, Dynamics, Pharmacokinetics, and <i>miR-21 rs1292037</i> Genotyping

Background and aim: The COVID-19 pandemic, caused by SARS-CoV-2, remains a global health crisis despite vaccination efforts, necessitating novel therapeutic strategies. Natural compounds from <i>Syzygium aromaticum</i> (clove), such as eugenol and β-caryophyllene, exhibit antiviral and a...

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Main Authors: Mustafa Ahmed Muhmood, Faiza Safi, Mohammed Mukhles Ahmed, Safaa Abed Latef Almeani
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Viruses
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Online Access:https://www.mdpi.com/1999-4915/17/7/951
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author Mustafa Ahmed Muhmood
Faiza Safi
Mohammed Mukhles Ahmed
Safaa Abed Latef Almeani
author_facet Mustafa Ahmed Muhmood
Faiza Safi
Mohammed Mukhles Ahmed
Safaa Abed Latef Almeani
author_sort Mustafa Ahmed Muhmood
collection DOAJ
description Background and aim: The COVID-19 pandemic, caused by SARS-CoV-2, remains a global health crisis despite vaccination efforts, necessitating novel therapeutic strategies. Natural compounds from <i>Syzygium aromaticum</i> (clove), such as eugenol and β-caryophyllene, exhibit antiviral and anti-inflammatory properties, while host genetic factors, including miR-21 rs1292037 polymorphism, may influence disease susceptibility and severity. This study investigates the dual approach of targeting SARS-CoV-2 via <i>Syzygium aromaticum</i> phytoconstituents while assessing the role of <i>miR-21 rs1292037</i> in COVID-19 pathogenesis. Methods: Firstly, molecular docking and molecular dynamics simulations were employed to assess the binding affinities of eugenol and caryophyllene against seven key SARS-CoV-2 proteins—including Spike-RBD, 3CLpro, and RdRp—using SwissDock (AutoDock Vina) and the Desmond software package, respectively. Secondly, GC-MS was used to characterize the composition of clove extract. Thirdly, pharmacokinetic profiles were predicted using in silico models. Finally, miR-21 rs1292037 genotyping was performed in 100 COVID-19 patients and 100 controls, with cytokine and coagulation markers analyzed. Results: Docking revealed strong binding of eugenol to viral Envelope Protein (−5.267 kcal/mol) and caryophyllene to RdRp (−6.200 kcal/mol). ADMET profiling indicated favorable absorption and low toxicity. Molecular dynamics simulations confirmed stable binding of methyl eugenol and caryophyllene to SARS-CoV-2 proteins, with caryophyllene–7Z4S showing the highest structural stability, highlighting its strong antiviral potential. Genotyping identified the TC genotype as prevalent in patients (52%), correlating with elevated IL-6 and D-dimer levels (<i>p</i> ≤ 0.01), suggesting a hyperinflammatory phenotype. Males exhibited higher ferritin and D-dimer (<i>p</i> < 0.0001), underscoring sex-based disparities. Conclusion: The bioactive constituents of <i>Syzygium aromaticum</i> exhibit strong potential as multi-target antivirals, with molecular simulations highlighting caryophyllene’s particularly stable interaction with the 7Z4S protein. Methyl eugenol also maintained consistent binding across several SARS-CoV-2 targets. Additionally, the miR-21 rs1292037 polymorphism may influence COVID-19 severity through its role in inflammatory regulation. Together, these results support the combined application of phytochemicals and genetic insights in antiviral research, pending further clinical verification.
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spelling doaj-art-e568a74deea243f4a41fcbcec44bcdec2025-08-20T02:47:09ZengMDPI AGViruses1999-49152025-07-0117795110.3390/v17070951<i>Syzygium aromaticum</i> Phytoconstituents Target SARS-CoV-2: Integrating Molecular Docking, Dynamics, Pharmacokinetics, and <i>miR-21 rs1292037</i> GenotypingMustafa Ahmed Muhmood0Faiza Safi1Mohammed Mukhles Ahmed2Safaa Abed Latef Almeani3Department of Biology, Faculty of Science, University of Sfax, Sfax 3029, TunisiaDepartment of Pediatrics, Hedi Chaker Hospital, Faculty of Medicine, University of Sfax, Sfax 3029, TunisiaDepartment of Biotechnology, Faculty of Science, University of Anbar, Anbar 31001, IraqDepartment of Biotechnology, Faculty of Science, University of Anbar, Anbar 31001, IraqBackground and aim: The COVID-19 pandemic, caused by SARS-CoV-2, remains a global health crisis despite vaccination efforts, necessitating novel therapeutic strategies. Natural compounds from <i>Syzygium aromaticum</i> (clove), such as eugenol and β-caryophyllene, exhibit antiviral and anti-inflammatory properties, while host genetic factors, including miR-21 rs1292037 polymorphism, may influence disease susceptibility and severity. This study investigates the dual approach of targeting SARS-CoV-2 via <i>Syzygium aromaticum</i> phytoconstituents while assessing the role of <i>miR-21 rs1292037</i> in COVID-19 pathogenesis. Methods: Firstly, molecular docking and molecular dynamics simulations were employed to assess the binding affinities of eugenol and caryophyllene against seven key SARS-CoV-2 proteins—including Spike-RBD, 3CLpro, and RdRp—using SwissDock (AutoDock Vina) and the Desmond software package, respectively. Secondly, GC-MS was used to characterize the composition of clove extract. Thirdly, pharmacokinetic profiles were predicted using in silico models. Finally, miR-21 rs1292037 genotyping was performed in 100 COVID-19 patients and 100 controls, with cytokine and coagulation markers analyzed. Results: Docking revealed strong binding of eugenol to viral Envelope Protein (−5.267 kcal/mol) and caryophyllene to RdRp (−6.200 kcal/mol). ADMET profiling indicated favorable absorption and low toxicity. Molecular dynamics simulations confirmed stable binding of methyl eugenol and caryophyllene to SARS-CoV-2 proteins, with caryophyllene–7Z4S showing the highest structural stability, highlighting its strong antiviral potential. Genotyping identified the TC genotype as prevalent in patients (52%), correlating with elevated IL-6 and D-dimer levels (<i>p</i> ≤ 0.01), suggesting a hyperinflammatory phenotype. Males exhibited higher ferritin and D-dimer (<i>p</i> < 0.0001), underscoring sex-based disparities. Conclusion: The bioactive constituents of <i>Syzygium aromaticum</i> exhibit strong potential as multi-target antivirals, with molecular simulations highlighting caryophyllene’s particularly stable interaction with the 7Z4S protein. Methyl eugenol also maintained consistent binding across several SARS-CoV-2 targets. Additionally, the miR-21 rs1292037 polymorphism may influence COVID-19 severity through its role in inflammatory regulation. Together, these results support the combined application of phytochemicals and genetic insights in antiviral research, pending further clinical verification.https://www.mdpi.com/1999-4915/17/7/951COVID-19<i>Syzygium aromaticum</i>eugenolcaryophyllenemolecular dockingmiR-21 rs1292037
spellingShingle Mustafa Ahmed Muhmood
Faiza Safi
Mohammed Mukhles Ahmed
Safaa Abed Latef Almeani
<i>Syzygium aromaticum</i> Phytoconstituents Target SARS-CoV-2: Integrating Molecular Docking, Dynamics, Pharmacokinetics, and <i>miR-21 rs1292037</i> Genotyping
Viruses
COVID-19
<i>Syzygium aromaticum</i>
eugenol
caryophyllene
molecular docking
miR-21 rs1292037
title <i>Syzygium aromaticum</i> Phytoconstituents Target SARS-CoV-2: Integrating Molecular Docking, Dynamics, Pharmacokinetics, and <i>miR-21 rs1292037</i> Genotyping
title_full <i>Syzygium aromaticum</i> Phytoconstituents Target SARS-CoV-2: Integrating Molecular Docking, Dynamics, Pharmacokinetics, and <i>miR-21 rs1292037</i> Genotyping
title_fullStr <i>Syzygium aromaticum</i> Phytoconstituents Target SARS-CoV-2: Integrating Molecular Docking, Dynamics, Pharmacokinetics, and <i>miR-21 rs1292037</i> Genotyping
title_full_unstemmed <i>Syzygium aromaticum</i> Phytoconstituents Target SARS-CoV-2: Integrating Molecular Docking, Dynamics, Pharmacokinetics, and <i>miR-21 rs1292037</i> Genotyping
title_short <i>Syzygium aromaticum</i> Phytoconstituents Target SARS-CoV-2: Integrating Molecular Docking, Dynamics, Pharmacokinetics, and <i>miR-21 rs1292037</i> Genotyping
title_sort i syzygium aromaticum i phytoconstituents target sars cov 2 integrating molecular docking dynamics pharmacokinetics and i mir 21 rs1292037 i genotyping
topic COVID-19
<i>Syzygium aromaticum</i>
eugenol
caryophyllene
molecular docking
miR-21 rs1292037
url https://www.mdpi.com/1999-4915/17/7/951
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