Agathis robusta Bark Essential Oil Effectiveness against COVID-19: Chemical Composition, In Silico and In Vitro Approaches

Abstract

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2), the causative agent of Coronavirus Disease 2019 (COVID-19), has seriously threatened global health. Alongside the approved vaccines, the discovery of prospective anti-COVID-19 drugs has been progressively targeted. Essential oils (EOs) provide a rich source of compounds with valuable antiviral activities that may contribute as effective agents against COVID-19. In this study, the EO of Agathus robusta bark was investigated for its chemical composition and its antiviral activity against SARS-CoV2. Overall, 26 constituents were identified by gas chromatography-mass spectrometry (GC-MS) analysis. α-Pinene, tricyclene, α-terpineol, limonene, d-camphene, trans-pinocarveol, α-phellandren-8-ol, L-β-pinene and borneol were the major components. In silico docking of these constituents against viral key enzymes, spike receptor-binding domain (RBD), main protease (Mpro) and RNA-dependent RNA polymerase (RdRp), using Molecular Operating Environment (MOE) software revealed good binding affinities of the components to the active site of the selected targets, especially, the RBD. In Vitro antiviral MTT and cytopathic effect inhibition assays demonstrated a promising anti SARS-CoV2 for A. robusta bark EO, with a significant selectivity index of 17.5. The results suggested using this EO or its individual components for the protection against or treatment of COVID-19.

Agathis robusta Bark Extract Protects from Renal Ischemia-Reperfusion Injury: Phytochemical, In Silico and In Vivo Studies

“…Few phytochemical studies have been conducted on A. robusta . These studies have mainly focused on the investigation of the essential oil composition and diterpenoid content [ 7 , 8 , 9 , 10 , 11 , 12 ]. Besides, only one phytochemical analysis was conducted for the ethanolic leaf extract of A. robusta , resulting in the isolation and identification of six compounds; agathisflavone, 7″- O -methyl-agathisflavone, cupressuflavone, rutin, shikimic acid, and (2S)-1,2-Di- O -[(9Z,12Z,15Z)-octadeca-9,12,15-trienoyl]-3- O - β -d-galactopyranosylglycerol [ 13 ].…”

“…Moreover, few studies explored the biological activities of this species, revealing that the leaf ethanolic extract possesses a considerable anti-inflammatory activity, while the essential oil has an antibacterial effect [ 7 , 14 ]. Recently, the bark essential oil of A. robusta has been shown to have antiviral activity against SARS-CoV2 [ 12 ]. However, no previous works about the total phytochemical composition of A. robusta bark extract nor its possible biological activities have been performed.…”

The Main Protease of SARS-CoV-2 as a Target for Phytochemicals against Coronavirus

“…Khaerunnisa S. et al extended the list with kaempferol, quercetin, luteolin-7-glucoside, demetoxycurcumine, naringenin, apigenin-7-glucoside, oleuropein, catechin, curcumin, zingerol, gingerol, and allicin [ 42 ]. Essential oils have also shown their effectiveness against SARS-CoV-2 Mpro in silico [ 43 , 44 , 45 ]. Therefore, using this approach, multiple natural compounds have been identified as strong binders of SARS-CoV-2 Mpro, and some of them were also identified as multi-target inhibitors that could be applied in COVID-19 management approaches [ 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ].…”

“…Essential oils have also shown their effectiveness against SARS-CoV-2 Mpro in silico [ 43 , 44 , 45 ]. Therefore, using this approach, multiple natural compounds have been identified as strong binders of SARS-CoV-2 Mpro, and some of them were also identified as multi-target inhibitors that could be applied in COVID-19 management approaches [ 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ].…”

Characterization of Terpenoids From Pseudognaphalium Gaudichaudianum (Dc) Anderb, Wira-Wira by Gc/Ms, Active Principles With Possible Use in Covid-19 Infection Prevention

“…They are also present in P. gaudichaudianum, as well as other major compounds like β-Eudesmene, Rosifoliol, β-Eudesmol and γ-Eudesmol, which are eudesmane sesquiterpenes. Other eudesmane derivatives, guaiol and α-Pinene (present in several essential oils) through in vitro and in silico experiments, showed a promising anti-SARS-CoV-2 activity due to a potential inhibitory effect on the protease Mpro of the virus [26][27][28][29][30]. These compounds could suggest that the essential oil from P. gaudichaudianum may have inhibitory activity.…”