In a recent study published in Moleculesresearchers assessed the likely efficacy of tea tree oil (TTO) as a natural disinfectant against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using the human coronavirus OC43 (HCoV-OC43) and feline coronavirus (FCoVII) as surrogate models.
SARS-CoV-2 can be transmitted in the air or through contact with contaminated surfaces; therefore, effective disinfectants are essential to minimize exposure to SARS-CoV-2. Melaleuca alternifolia or TTO has been reported to have antiviral, antibacterial and antifungal properties. It has been proposed that TTO can inhibit entry to SARS-CoV-2 and affect the structural dynamics of the SARS-CoV-2 membrane and its envelope components.
About the study
In the present study, researchers evaluated whether TTO could potentially be used as an effective disinfectant to limit SARS-CoV-2 contamination by assessing TTO efficacy using FCoVII and HCoV-OC43 as surrogate models.
First the in vitro virucidal activity of TTO and its three major compounds (γ-terpinene, 1,8-cineole and terpinen-4-ol) was assessed using an alpha-coronavirus, FCoVII, and a beta-coronavirus, HCoV-OC43. For the analysis, 5 log ribonucleic acid (RNA) copies/ml HCoV-OC43 and 6 log median tissue culture infectious dose (TCID50/ml) FCoVII were used with different dilutions of TTO-EtOH for five minutes, 15 minutes and 30 minutes.
In addition, the likely activity of TTO against SARS-CoV-2 was assessed using Gaussian accelerated molecular dynamics simulations (GaMD) and a in silico approach, for which the SARS-CoV-2 spike (S) protein was simulated and examined in the absence or presence of the three major TTO components. The antiviral activities of the three major TTO components were also independently evaluated against HCoV-OC43 and FCoVII. Furthermore, the virucidal activity of TTO was compared with that of a commonly used disinfectant (ISACLEAN), comprising benzalkonium chloride (50%), isazone, isopropanol and chlorhexidine gluconate.
Formulation A, comprising 3.3% TTO and 5.3% EtOH, was highly virucidal. It inhibited FCoVII replication in CRFK cells with a reduction of at least 3.5 log TCID50/ml in the feline coronavirus titers within five minutes. Similar findings were obtained after 15 minutes and 30 minutes FCoVII contact with the same formulation. In contrast, for formulations B and C (with lower concentrations), no or moderate virucidal activity against FCoVII was observed.
Similarly, a decrease of 1.4 log RNA copies/ml HCoV-OC43 was achieved after 30 minutes using formulation A, with moderate virucidal effects against HCoV-OC43 using formulations B and C. At a TTO concentration of 3 .3% the HCoV-OC43 activity was inhibited, while no substantial effects were observed at the other concentrations from 0.7%.
On the contrary, formulation D (5.3% EtOH) did not inhibit the replication of HCoV-OC43 and FCoVII in vitro† Within five minutes of contact, the commonly used disinfectant caused ≥99% inactivation of FCoVII and HCoV-OC43, comparable to the effects of TTO Formulation A against HCoV-OC43 and FCoVII after 30 minutes and five minutes of contact, respectively.
At a concentration of 3.3%, all three major TTO components exhibited robust antiviral effects against both the surrogate coronaviruses, with 1.0 log (90%) and 0.9 log (87.1%) reductions in FCoVII and HCoV-OC43 titers, respectively, within 15 minutes of -terpinene contact. Note that after 30 min of exposure, a log reduction of ≥ 1.0 was observed for both surrogate coronaviruses when exposed to γ-terpinene, which represented 90% of virus inactivation.
However, at a concentration of γ-terpinene of 0.7%, a ≥90% decrease in titers was observed for HCoV-OC43 alone after 30 minutes of exposure, while the effects on FCoVII were less. A concentration of 3.3% 1,8-cineole resulted in a >90% reduction in HCoV-OC43 titres within five minutes of exposure. However, at a concentration of 0.7% and a contact of 30 minutes, the activity of the compound was decreased and the virus titers were decreased by 85.5% (0.8 log).
Of note, terpinen-4-ol was the most virucidal of all three TTO components against the surrogate coronaviruses, at a concentration of 3.3% and at all time points (five minutes, 15 minutes, and 30 minutes), with a ( ≥99 %) (≥2.2 log) reduction in viral titers within just five minutes of contact. Terpinen-4-ol showed less effects against the surrogate coronavirus models, with a 90% decrease in FCoVII titres and a 77% decrease in HCoV-OC43 titres after 30 minutes of contact.
In the second GaMD phase (from 100 ns to the end of simulations), the membrane thickness of SARS-CoV-2 increased by 0.7 in the presence of TTO. While all three major TTO components had been introduced into the membrane, γ-terpinene reached the opposing membrane sheet, showed lateral movements and was most persistently bound to the S surface. Analysis of radial distribution functions (RDFs) showed a sharp peak in -terpinene density at 0.8 to 1.9 nm from the S protein.
The γ-terpinene binding site corresponded to fatty acid residues (FA) 330 to 470 and 500 to 515 of SARS-CoV-2 S, and the binding of γ-terpinene (and other TTO components) reduced SARS-CoV-2 S binding angiotensin host converting enzyme 2 (ACE2). The TTO compounds could also cause steric hindrance of S subunit 2 (S2) protease interactions and showed transient binding to the HR2 helix bundle residues 1163 to 1202.
For the S1 and S2 subunits, increased negatively correlated movements and decreased positively correlated movements were observed with TTO. The N-terminal domains (NTDs), receptor binding domains (RBDs) and C-terminal domains (CTDs) of SARS-CoV-2S showed the appearance and disappearance of many salt bridges in the presence of TTO. However, 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.
Overall, the study results showed that TTO could be a potential disinfectant to limit the transmission of SARS-CoV-2, based on the virucidal activity of TTO against FCoVII and HCoV-OC43 and changes in the physical properties and structural organization of the SARS-CoV-2 envelope.
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