From ancient remedy to modern medicine: Artemisia argyi sesquiterpenoids as a promising natural treatment for COVID-19

[Display omitted] •UPLC-Q-Exactive-Orbitrap MS analysis identified 69 in Artemisia argyi sesquiterpenoids (AASs), with 17 compounds isolated.•Network pharmacology analysis was used to obtain seven core targets of A. argyi sesquiterpenoids in COVID-19 and the major signaling pathways involved.•Sesquiterpenes with O-diol hydroxyl in the five-membered ring structure of guaiacane lactone are beneficial to inhibit the activity of Mpro, while the structures of α, β-unsaturated-γ-lactone and unsaturated ketone form stable hydrogen bonds with iNOS to inhibit the secretion of NO.•Several AASs compounds were found to be effective in inhibiting SARS-CoV-2 and reducing inflammation, with Compound 10 (Achillinin C) identified as a promising compound that effectively inhibited the virus and reduced inflammation without impacting normal cell growt. Artemisia argyi H. Lév. & Vaniot (A. argyi), a traditional Chinese herbal medicine, has been commonly used in plague epidemics and has bactericidal and sterilizing pharmacological effects. This study aimed to investigate the chemical composition and molecular mechanism of A. argyi, specifically focusing on its main active components, sesquiterpenoids. A total of 69 sesquiterpenoids were identified by UPLC-Q-Exactive-Orbitrap MS, of which 17 compounds were isolated. By integrating multiple databases, 91 overlapping protein targets were found between A. argyi sesquiterpenes and COVID-19, and 7 core targets and major signaling pathways for disease treatment were suggested. The techniques of SARS-CoV-2 pseudovirus (PsV) infection, fluorescence resonance energy transfer (FRET) and Surface plasmon resonance (SPR) have shown that some compounds in A. argyi can effectively inhibit PsV infection and the activities of Mpro and RBD and exert anti-inflammatory effects by reducing the secretion of NO. Molecular docking further confirmed the binding ability of these compounds to the corresponding proteins. It was found that Compound 10 (Achillinin C) could significantly inhibit the infection of PsV at a concentration of 14.85 μM, showing an anti-inflammatory effect and no obvious cytotoxicity to a variety of cells at this concentration. The study concludes that A. argyi holds promise as a natural treatment for COVID-19, offering multiple sesquiterpenoids with potential antiviral and anti-inflammatory properties. These findings provide a solid foundation for future research on traditional Chinese medicine for epidemic prevention.