A recent study conducted by scientists from multiple universities in Saudi Arabia and Egypt has explored the potential of natural phenolic acids in inhibiting SARS-CoV-2, the virus responsible for COVID-19. Phenolic acids are secondary metabolites found in various plants and are known for their diverse health benefits. The researchers focused on two important targets in the virus’s life cycle: the main protease (Mpro) and adaptor-associated protein kinase 1 (AAK1). Inhibiting these targets can potentially halt the virus’s progression within the host.
To evaluate the inhibitory potential of natural phenolic acids, the researchers used pharmacophore mapping and molecular docking studies. Rosmarinic acid and 2,3-dihydroxybenzoic-5-O-glucoside showed promise in inhibiting Mpro, while tannic acid exhibited the most favorable binding energy for AAK1. Molecular dynamics simulations further supported the stability of these phenolic acid-protein complexes over time.
Principal component analysis was used to explore the conformational distribution and large-scale collective motions of the protein-ligand complexes. The Mpro-rosmarinic acid complex demonstrated a more stable interaction compared to the AAK1-tannic acid complex.
An ADME study assessed the bioavailability and toxicity of the selected compounds. Some phenolic acids showed good gastrointestinal absorption, but modifications may be needed to improve the bioavailability of tannic acid and rosmarinic acid. The tested compounds were found not to be substrates for cell efflux, indicating they are unlikely to be expelled from cells. Toxicity studies indicated that tannic acid and rosmarinic acid were non-carcinogenic and non-mutagenic.
The study highlights the potential of natural phenolic acids, particularly rosmarinic acid and tannic acid, as promising candidates for inhibiting key proteins in the SARS-CoV-2 life cycle. Their strong binding affinities, stability, and low toxicity profiles make them attractive options for further research as potential treatments for COVID-19. However, additional research is needed to confirm their efficacy and safety in human subjects. The pursuit of natural compounds as antiviral agents remains an important area of research in the fight against COVID-19. The study findings were published in the peer-reviewed journal Scientific Reports.