Phytochemical Inhibitors of SARS‐CoV‐2 Entry: Targeting the ACE2‐RBD Interaction with <scp>l</scp>‐Tartaric Acid, <scp>l</scp>‐Ascorbic Acid, and <i>Curcuma longa</i> Extract

Abstract

Abstract Phytochemicals are emerging as promising antiviral agents with the potential to address both acute and long‐term complications of viral infections such as COVID‐19. SARS‐CoV‐2, the virus responsible for COVID‐19, enters host cells by binding its spike protein's receptor‐binding domain (RBD) to the angiotensin‐converting enzyme‐2 (ACE2) receptor. Inhibiting this interaction may provide new therapeutic approaches. This study aimed to evaluate the inhibitory effects of Curcuma longa extract, l ‐ascorbic acid, and l ‐tartaric acid on the ACE2‐RBD interaction and to explore their potential as antiviral agents against SARS‐CoV‐2. A competitive ELISA was used to assess the inhibitory activity on the ACE2‐RBD interaction, with l ‐tartaric acid showing the strongest inhibition (IC50 = 0.009 mg/ml). C. longa extract displayed dose‐dependent inhibition, while l ‐ascorbic acid showed peak inhibition between 0.4 and 1 mg/mL. Molecular docking and 100 ns molecular dynamics simulations confirmed strong and stable interactions involving curcuminoids with ACE2. These findings underscore the potential of these compounds to function as effective SARS‐CoV‐2 entry inhibitors, supporting their further investigation as promising therapeutic candidates.