Phytochemical Inhibitors of SARS-CoV-2 Entry: Targeting the ACE2-RBD Interaction with l-Tartaric Acid, l-Ascorbic Acid, and Curcuma longa Extract

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.