In a recent study published in Moleculesthe researchers assessed the likelihood efficiency of tea tree oil (TTO) as a natural disinfectant against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using human coronavirus OC43 (HCoV-OC43) and feline coronavirus (FCoVII) as models of substitution.
SARS-CoV-2 can be transmitted through the air or through contact with contaminated surfaces; therefore, effective disinfectants are essential to minimize exposure to SARS-CoV-2. Melaleuca alternifolia or TTO is said to have antiviral, antibacterial and antifungal properties. It has been proposed that TTO may inhibit SARS-CoV-2 entry and influence the structural dynamics of SARS-CoV-2 membrane and envelope constituents.
About the study
In the present study, researchers assessed whether TTO could potentially be used as an effective disinfectant to limit SARS-CoV-2 contamination by evaluating the effectiveness of TTO using FCoVII and HCoV-OC43 as surrogate models.
First the in vitro the virucidal activity of TTO and its three main compounds (γ-terpinene, 1,8-cineole and terpinene-4-ol) was evaluated using an alphacoronavirus, FCoVII, and a beta coronavirus, HCoV-OC43. For analysis, 5 log ribonucleic acid (RNA) copies/mL of HCoV-OC43 and 6 log median tissue culture infectious dose (TCID50/mL) of FCoVII were used with different dilutions of TTO-EtOH for five minutes, 15 minutes and 30 minutes.
Additionally, the likely activity of TTO against SARS-CoV-2 was assessed using Gaussian accelerated molecular dynamics (GaMD) simulations and a silicone 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 main components of TTO were also independently assessed against HCoV-OC43 and FCoVII. Additionally, the virucidal activity of TTO was compared to that of a commonly used disinfectant agent (ISACLEAN), which included 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 minimal 3.5 Log TCID50/mL reduction in feline coronavirus titers within five minutes. Similar results were obtained after 15 minutes and 30 minutes of FCoVII contact with the same formulation. On the other hand, for formulations B and C (with lower concentrations), no virucidal or moderate activity against FCoVII was observed.
Similarly, a decrease of 1.4 Log RNA copies/mL of HCoV-OC43 was achieved after 30 minutes using formulation A, with moderate virucidal effects against HCoV-OC43 using formulations B and C. a concentration of 3.3% TTO, HCoV-OC43 activity was inhibited. , while no substantial effect was observed with 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 disinfecting agent induced ≥99% inactivation of FCoVII and HCoV-OC43, similar 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%, the three major components of TTO demonstrated robust antiviral effects against the surrogate coronavirus, with 1.0 Log (90%) and 0.9 Log (87.1%) reductions in FCoVII and HCoV-OC43 titers, respectively, within 15 minutes of contact with γ-terpinene. Of note, after 30 min of exposure, a ≥1.0 log reduction was noted for both surrogate coronaviruses upon exposure to γ-terpinene, which accounted for ≥90% of the inactivation of the virus.
However, at a concentration of 0.7% γ-terpinene, a ≥90% decrease in titers was observed only for HCoV-OC43 after 30 minutes of exposure, whereas effects on FCoVII were less. A 3.3% concentration of 1,8-cineole resulted in a >90% reduction in HCoV-OC43 titers within five minutes of exposure. Yet, at 0.7% concentration and 30 minutes of contact, compound efficacy was reduced and virus titers were reduced by 85.5% (0.8 log).
Interestingly, terpinene-4-ol was the most virucidal of the three components of TTO against surrogate coronaviruses, at the 3.3% concentration and at all time points (five minutes, 15 minutes, and 30 minutes), with a (≥99%) (≥2.2 Log) reduction in viral titers in just five minutes of contact. Terpinene-4-ol demonstrated lesser effects against surrogate coronavirus models, with a 90% decrease in FCoVII titers and a 77% decrease in HCoV-OC43 titers after 30 minutes of contact.
In the second GaMD phase (from 100 ns until the end of the simulations), the membrane thickness of SARS-CoV-2 increased by 0.7 Å in the presence of TTO. While the three major components of TTO were inserted into the membrane, γ-terpinene reached the opposite membrane leaflet, showed lateral movements, and was most persistently bound to the S surface. radial distribution (RDF) showed a sharp peak in γ-terpinene density at 0.8–1.9 nm from protein S.
The γ-terpinene binding site corresponded to fatty acid (FA) residues 330–470 and 500–515 of SARS-CoV-2S, and binding of γ-terpinene (and other TTO components) decreased binding of the SARS-CoV-2 S angiotensin converting enzyme 2 (ACE2) to the host. TTO compounds could also cause steric hindrance of S2 subunit (S2)-protease interactions and showed transient binding to residues 1163–1202 of the HR2 helix bundle.
For the S1 and S2 subunits, an increase in negatively correlated movements and a decrease in positively correlated movements were observed with TTO. N-terminal domains (NTDs), receptor-binding domains (RBDs), and C-terminal domains (CTDs) of SARS-CoV-2S showed the appearance and disappearance of numerous 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] demonstrated great 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 alterations in the physical properties and structural organization of the SARS-CoV-2 envelope.
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