{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:58:11Z","timestamp":1787317091188,"version":"build-2736575974"},"reference-count":48,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,5]],"date-time":"2025-07-05T00:00:00Z","timestamp":1751673600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>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 Syzygium aromaticum (clove), such as eugenol and \u03b2-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 Syzygium aromaticum phytoconstituents while assessing the role of miR-21 rs1292037 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\u2014including Spike-RBD, 3CLpro, and RdRp\u2014using 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 (\u22125.267 kcal\/mol) and caryophyllene to RdRp (\u22126.200 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\u20137Z4S 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 (p \u2264 0.01), suggesting a hyperinflammatory phenotype. Males exhibited higher ferritin and D-dimer (p &lt; 0.0001), underscoring sex-based disparities. Conclusion: The bioactive constituents of Syzygium aromaticum exhibit strong potential as multi-target antivirals, with molecular simulations highlighting caryophyllene\u2019s 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.<\/jats:p>","DOI":"10.3390\/v17070951","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T11:19:27Z","timestamp":1751887167000},"page":"951","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Syzygium aromaticum Phytoconstituents Target SARS-CoV-2: Integrating Molecular Docking, Dynamics, Pharmacokinetics, and miR-21 rs1292037 Genotyping"],"prefix":"10.3390","volume":"17","author":[{"given":"Mustafa Ahmed","family":"Muhmood","sequence":"first","affiliation":[{"name":"Department of Biology, Faculty of Science, University of Sfax, Sfax 3029, Tunisia"},{"name":"Department of Medical Laboratory Techniques, University of Al-Ma\u2019aref, Anbar 31001, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faiza","family":"Safi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hedi Chaker Hospital, Faculty of Medicine, University of Sfax, Sfax 3029, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2831-9246","authenticated-orcid":false,"given":"Mohammed Mukhles","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Faculty of Science, University of Anbar, Anbar 31001, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Safaa Abed Latef","family":"Almeani","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Faculty of Science, University of Anbar, Anbar 31001, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Silva, R.C., Freitas, H.F., Campos, J.M., Kimani, N.M., Silva, C.H.T.P., Borges, R.S., Pita, S.S.R., and Santos, C.B.R. 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