Antimicrobial Potential of Commercially Produced Citronella Oil: An In Vitro and In Silico Investigation

Introduction: Antimicrobial resistance poses a significant global health threat in the 21st century. The COVID-19 pandemic, caused by SARS-CoV-2, has further emphasized the need for novel and effective alternative therapeutics, especially from natural sources. Despite the known bioactivity of citronella oil, its potential as a broad-spectrum antimicrobial and antiviral agent remains underexplored. This study aimed to evaluate the antibacterial, antifungal, and anti-viral potential of commercially produced citronella oil using in vitro and in silico approaches. Methods: The chemical constituents of citronella oil were identified using gas chromatography-mass spectrometry (GC-MS). Antibacterial activity was assessed using the disk diffusion method, while antifungal efficacy was evaluated via the poison plate method. In silico techniques, includ-ing molecular docking, ADMET profiling, density functional theory, molecular dynamics simula-tion, principal component analysis, and dynamic cross-correlation mapping, were used to predict antiviral activity against the SARS-CoV-2 main protease (Mpro). Results: GC-MS identified 30 compounds in citronella oil. Antibacterial assays demonstrated no-table inhibition against Bacillus cereus (32 μL/mL), Staphylococcus aureus (128 μL/mL), Esche-richia coli (8 μL/mL), and Klebsiella pneumoniae (32 μL/mL). The oil achieved 100% mycelial growth inhibition of Fusarium oxysporum at 70 μL/mL. Molecular docking identified three com-pounds- CID-91697, CID-5367548, and CID-609268- with higher binding affinities than the ref-erence drug shikonin. Computational analyses highlighted CID-91697 as the most promising can-didate for SARS-CoV-2 Mpro inhibition. Discussion: The results show that commercially available citronella oil has strong antifungal properties and moderate antibacterial properties. This suggests that it could be a natural broad-spectrum antimicrobial agent. Furthermore, in silico analyses indicate that CID-91697 may func-tion as a potential inhibitor of SARS-CoV-2 Mpro, thus underscoring its significance in antiviral drug discovery. Overall, the results from both in vitro and computer-based studies make a solid case for further preclinical research. Conclusion: This study presents the first report on the therapeutic potential of commercially produced citronella oil from Bangladesh as a dual-purpose antimicrobial and antiviral agent. The antifungal potential of citronella oil surpassed its antibacterial efficacy against the tested strains, and CID-91697 is recommended as a promising lead compound against SARS-CoV-2 according to the outcomes of in silico studies. These findings support further experimental and clinical validation of citronella oil as a sustainable, natural alternative for combating infectious diseases.