Metabolic Screening and In Silico Investigation of Eucalyptus globulus Essential Oil Bioactives Against DENV‐2 Envelope Protein

The escalating prevalence of viral infectious diseases poses a significant threat to global public health. Among these, dengue virus (DENV) represents one of the most widespread arboviral infections, impacting nearly 400 million individuals annually, with severe clinical manifestations occurring in approximately 1% of cases, as reported by the World Health Organization (WHO). Extensive research across both academic and industrial sectors has focused on various aspects of DENV, including its molecular virology, epidemiological patterns, transmission pathways, and therapeutic targets. The development of the tetravalent CYD‐TDV (Dengvaxia) vaccine marked a critical advancement in dengue prevention. Nonetheless, emerging evidence has highlighted several limitations associated with current vaccination strategies, prompting a growing emphasis on the discovery and development of antiviral agents as alternative or complementary therapeutic options for effective dengue management. A total of 14 major bioactive compounds were found to be highly correlated with Dengue, yielding 70 common targets between dengue and bioactive compounds. Protein–protein interaction and network pathway analysis by KEGG and Metascape analysis show higher degree of correlation for DENV‐2 targets. Molecular docking analysis shows that Globulol and Ecalyptol have higher binding affinity with two receptors, 1oke and 1tg8 f DENV‐2, with binding energies of −8.3 and −7.6. Toxicity and drug‐likeness analyses confirmed the safety of the metabolites for drug development. These findings suggest that Eucalyptus globulus essential oil may have potential in the treatment of dengue fever. However, further in vivo studies using animal models are required to validate its therapeutic efficacy.