Role of tannic acid against SARS-cov-2 cell entry by targeting the interface region between S-protein-RBD and human ACE2

Abstract

Coronavirus disease 2019 (COVID-19) was caused by a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 utilizes human angiotensin converting enzyme 2 (hACE2) as the cellular receptor of its spike glycoprotein (SP) to gain entry into cells. Consequently, we focused on the potential of repurposing clinically available drugs to block the binding of SARS-CoV-2 to hACE2 by utilizing a novel artificial-intelligence drug screening approach. Based on the structure of S-RBD and hACE2, the pharmacophore of SARS-CoV-2-receptor-binding-domain (S-RBD) -hACE2 interface was generated and used to screen a library of FDA-approved drugs. A total of 20 drugs were retrieved as S-RBD-hACE2 inhibitors, of which 16 drugs were identified to bind to S-RBD or hACE2. Notably, tannic acid was validated to interfere with the binding of S-RBD to hACE2, thereby inhibited pseudotyped SARS-CoV-2 entry. Experiments involving competitive inhibition revealed that tannic acid competes with S-RBD and hACE2, whereas molecular docking proved that tannic acid interacts with the essential residues of S-RBD and hACE2. Based on the known antiviral activity and our findings, tannic acid might serve as a promising candidate for preventing and treating SARS-CoV-2 infection.

Antiviral Effects of Secondary Metabolites from Jatropha podagrica Leaves against the Pseudotyped Virus of SARS-CoV-2 Omicron

“…In addition, tannic acid has shown potent inhibition of main protease (Mpro)/3CLpro and TMPRSS2, which are essential proteins for the propagation of SARS-CoV-2 [69,70]. In particular, it was confirmed that tannic acid prevented pseudotyped SARS-CoV-2 entrance by preventing S-RBD from attaching to ACE2 [71,72]. Notably, orally administered tannic acid isomers have exhibited effectiveness against SARS-CoV-2 variants such as Delta and Omicron [73].…”