Existing challenges, such as the viral SARS-CoV-2 B.1.1.529 Omicron variants, adverse reactions, and limited availability of drugs for COVID-19 continue to challenge global health. Severe inflammatory response associated with COVID-19 has been shown to worsen diabetic conditions and finding a range of treatment options for COVID-19 is significant. The research investigated the potential of Plectranthus amboinicus (Lour.) Spreng. (Lamiaceae) essential oil (PEO), known for its bioactive terpene content, as a multifaceted therapeutic agent. In silico and in vitro approaches were conducted to evaluate its inhibitory effects on the replication of Omicron variant, its ability to modulate proinflammatory biomarkers, and its impact on diabetes-related enzymes. PEO was extracted by hydrodistillation method. GC-MS analysis revealed 62 compounds. In silico molecular docking showed that the top ten PEO major components exhibited strong binding affinities with Omicron 3CL protease (-4.0 to −6.1 kcal/mol) and spike-RBD protein (-6.1 to −9.2 kcal/mol). PEO (6.25–200 μg mL⁻¹) significantly inhibited the B.1.1.529 Omicron SARS-CoV-2 3CL protease and Spike-RBD. PEO showed a cytotoxic effect at >80 μg mL⁻¹ in LPS-induced macrophage and inhibited production of TNF-α from 6.25 to 50 μg mL⁻¹, indicating its potential to mitigate the cytokine storm in link with severe COVID-19 cases. In vitro, PEO at 6.25–200 μg mL⁻¹ significantly inhibited α-amylase and α-glucosidase enzymes, suggesting that PEO components could modulate key enzymes involved in glucose metabolisms. These findings showed the potential of PEO as an antiviral, anti-inflammatory, and antidiabetic agent and offer an opportunity to further clinical investigations in testing the efficacy as an alternative approach to managing COVID-19 and its complications.
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