Targeting angiotensin-converting enzyme 2 (ACE2) with bioactive compounds from Achillea ageratum essential oil: Chemical composition and first computational study for enhanced anti-SARS-CoV-2 therapy

In recent years, viral infections have regained global attention as major contributors of mortality worldwide, especially during the COVID-19 pandemic caused by SARS-CoV-2, a highly contagious respiratory virus. Angiotensin-converting enzyme-2 (ACE2) serves as the principal receptor mediating SARS-CoV-2 entry into host cells. Previous studies have reported the potential of essential oil (EO) compounds to target ACE2, encouraging further exploration of their anti-SARS-CoV-2 activity. In this work, we explored in silico the inhibitory effect of A. ageratum essential oil (AAEO) on SARS-CoV-2 entry by targeting ACE2. The EO was extracted via hydro-distillations using a Clevenger-type apparatus. Gas chromatography–mass spectrometry (GC-MS) analysis identified six major compounds: artemisyl acetate (53.21%), α-santalol (15.17%), yomogi alcohol (9.41%), santolina alcohol (5.62%), artemisia alcohol (4.48%), and artemisiatriene (2.41%). Following structural optimization, molecular docking was performed using Autodock Vina with the ACE2 receptor in complex with its co-crystallized. Docking analyses showed that α-santalol has a highest binding affinity with a binding energy of –6.27 kcal/mol and extensive hydrophobic interactions with critical residues of ACE2. However, absorption, distribution, metabolism, excretion, and toxicity analysis (ADMET) revealed that this molecule may cause respiratory system toxicity, whereas the other compounds demonstrated favourable pharmacokinetic and toxicological profiles. This work suggests that AAEO contains promising bioactive compounds against SARS-CoV-2, however; further chemical optimization and in vivo and in vitro testing are required to prove their therapeutic potential and evaluate their safety profile.