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

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 antiviral potential of commercially produced citronella oil using in vitro and in silico approaches.

The chemical constituents of citronella oil were identified using gas chromatographymass 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, including molecular docking, ADMET profiling, density functional theory, molecular dynamics simulation, principal component analysis, and dynamic cross-correlation mapping, were used to predict antiviral activity against the SARS-CoV-2 main protease (Mpro).

GC-MS identified 30 compounds in citronella oil. Antibacterial assays demonstrated notable inhibition against Bacillus cereus (32 μL/mL), Staphylococcus aureus (128 μL/mL), Escherichia 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 compounds- CID-91697, CID-5367548, and CID-609268- with higher binding affinities than the reference drug shikonin. Computational analyses highlighted CID-91697 as the most promising candidate for SARS-CoV-2 Mpro inhibition.

The results show that commercially available citronella oil has strong antifungal properties and moderate antibacterial properties. This suggests that it could be a natural broadspectrum antimicrobial agent. Furthermore, in silico analyses indicate that CID-91697 may function 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.

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.