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Study Shows Tea Tree Oil Can Prevent SARS-CoV-2 Transmission

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission could occur either in the air or by contact with contaminated surfaces. This warrants the need for efficient disinfectants for minimizing exposure to SARS-CoV-2.

Melaleuca alternifolia essential oil or tea tree oil (TTO) has been reported to possess antibacterial, antiviral, and antifungal properties. It has been proposed that TTO can inhibit the entry of SARS-CoV-2 into the host and can alter the structural dynamics of the SARS-CoV-2 envelope and membrane constituents. In a recent Molecules study, researchers explored the potential effectiveness of tea tree essential oil (TTO) as a natural disinfecting agent against SARS-CoV-2, using two surrogate models viz. the feline coronavirus (FCoVII) and the human coronavirus OC43 (HCoV-OC43)

About the study

The researchers of the present study determined whether TTO could be an effective natural disinfectant and limit SARS-CoV-2 contamination by evaluating TTO’s effectiveness using the FCoVII and the HCoV-OC43 as surrogate models in the analysis.

The in vitro virucidal activity of TTO and its three main constituents (γ-terpinene,terpinen-4-ol, and 1,8-cineole,) was evaluated using an alphacoronavirus, (FCoVII) and a beta coronavirus (HCoV-OC43). In the study, 6 Log median tissue culture infectious doses (TCID50/mL) of FCoVII and 5 Log ribonucleic acid (RNA) copies/mL of HCoV-OC43 were utilized with varying serial dilutions of TTO-EtOH for 5, 15, and 30 minutes.

Additionally, the potential activity of TTO against SARS-CoV-2 was determined using an in silico approach involving Gaussian accelerated molecular dynamic simulations (GaMD), for which, the spike (S) protein of SARS-CoV-2 was simulated and studied in the absence or presence of the three major TTO constituents. Further, the antiviral effect of the three main TTO constituents was also independently assessed against the two surrogate models. TTO virucidal efficacy was compared to that of ISACLEAN, a frequently used disinfectant that consisted of benzalkonium chloride (50%), isopropanol, chlorhexidine gluconate, and isazone,

Results of the study

Formulation A (3.3% TTO and 5.3% EtOH) showed robust virucidal activity and inhibited FCoVII replication in CRFK cells with at least 3.5 Log TCID50/mL reduction of the FCoVII titers within 5 minutes. Similar observations were found after 15 minutes and after 30 minutes of FCoVII contact with Formulation A. In contrast, for formulations B and C (of lower concentrations), moderate or no virucidal activity was observed against FCoVII.

Likewise, a reduction of 1.4 Log RNA copies/mL of HCoV-OC43 was observed after 30 minutes using formulation A, with moderate virucidal activity against HCoV-OC43 using formulations B and C. At 3.3% TTO concentration, HCoV-OC43 activity was inhibited, whereas no significant effects were found with the other TTO concentrations beginning from 0.7%.

On the contrary, formulation D (5.3% EtOH) could not inhibit HCoV-OC43 and FCoVII replication in vitro. After 5 minutes of contact, the commonly used disinfecting agent induced a ≥99% inactivation of both the surrogate models, identical to TTO formulation A effects against HCoV-OC43 and FCoVII after 30 minutes and 5 minutes of contact, respectively.

At 3.3% TTO concentration, all the three prime TTO constituents showed robust antiviral effects against both the surrogate coronaviruses, with 1.0 Log (90%) and 0.9 Log (87.1%) reductions in the FCoVII titers and titers of HCoV-OC43, respectively, within 15 minutes of γ-terpinene contact. Of note, after 30 minutes of exposure, ≥1.0 log reduction was noted for both surrogate coronaviruses on exposure to γ-terpinene, which accounted for ≥90% of virus inactivation.

However, at 0.7% concentration of γ-terpinene, a ≥90% decrease in titers was observed for only HCoV-OC43 post 30 minutes of exposure, whereas the effects on FCoVII were lower. A 3.3% 1,8-cineole concentration led to a >90% reduction in HCoV-OC43 titers in 5 minutes of exposure, but at 0.7% TTO concentration and 30 minutes of contact, the compound’s efficacy reduced, and SARS-CoV-2 titers decreased by 85.5% (0.8 Log difference).

Interestingly, terpinen-4-ol was the most virucidal of all three TTO constituents against both the surrogate coronavirus models, at the 3.3% concentration and at all the time points (5, 15, and 30 minutes), with a ≥99% (≥2.2 Log) reduction in SARS-CoV-2 titers within just 5 minutes of contact. Terpinen-4-ol showed lower virucidal effects against both the surrogate coronaviruses, with a 90% reduction in FCoVII titers and a 77% reduction in HCoV-OC43 titers after a 30-minute-contact.

In the second phase of GaMD analysis (from 100 ns till the end of simulations), the membrane SARS-CoV-2 thickened by 0.7 Å in the presence of TTO. While all the three main TTO constituents were inserted into the SARS-CoV-2 membrane, γ-terpinene reached the opposite membrane leaflet, demonstrated lateral movements, and was most persistently bound to the spike protein surface. In the radial distribution functions (RDFs) analysis, a sharp peak was observed in γ-terpinene density at 0.8 to 1.9 nm from the SARS-CoV-2 spike protein.

The binding site of γ-terpinene corresponded to fatty acid (FA) residues 330 to 470 and 500 to 515 of SARS-CoV-2 spike protein. γ-terpinene (and other TTO constituents) reduced SARS-CoV-2 S binding interactions with the host angiotensin-converting enzyme 2 (hACE2). The three main TTO constituents also caused steric hindrance of SARS-CoV-2 spike protein subunit 2 (S2) interactions with proteases and exhibited temporary binding with the heptad repeats (HR2) helix bundle residues 1163 to 1202.

Furthermore, for the S1 and S2 subunits of SARS-CoV-2 spike protein, more negatively correlated motions and less positively correlated motions were found in the presence of TTO. The receptor binding domains (RBDs, N-terminal domains (NTDs), and C-terminal domains (CTDs) of SARS-CoV-2 spike protein demonstrated the appearance and disappearance of several salt bridges in TTO presence, although five salt bridges [glutamic acid (Glu)169-lysine (Lys)129, aspartic acid (Asp)290-Arg273, Asp398-arginine (Arg)355, Asp442-Arg509 and Asp53-Lys195] showed high stability in the analysis.

Overall, the study findings demonstrated that tea tree essential oil could be a potential natural disinfecting agent for limiting SARS-CoV-2 transmission, based on the TTO virucidal effects observed against the FCoVII and HCoV-OC43 surrogate coronavirus models and altered structural dynamics and physical properties of the SARS-CoV-2 envelope.

Reference:

Romeo, A.; Iacovelli, F.; Scagnolari, C.; Scordio, M.; Frasca, F.; Condò, R.; Ammendola, S.; Gaziano, R.; Anselmi, M.; Divizia, M.; et al. Potential Use of Tea Tree Oil as a Disinfectant Agent against Coronaviruses: A Combined Experimental and Simulation Study. Molecules 2022, 27, 3786. https://doi.org/10.3390/ molecules27123786

Author

Pooja Toshniwal Paharia

Dr. Pooja Toshniwal Paharia is a Consultant Oral and Maxillofacial Physician and Radiologist, M.DS (Oral Medicine and Radiology) from Mumbai. She strongly believes in evidence-based radiodiagnosis and therapeutic regimens for benign, potentially malignant, or malignant lesions and conditions either arising from the oral and maxillofacial structures or manifesting in the associated regions.

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