Identifying compounds that prevent the binding of the SARS-CoV-2 S-protein to ACE2

Highlights

• We propose one compound (called ED) interacting in the ACE2, to reduce the interaction with the RBD. S

• We determined an IC₅₀ of 31.95 μM.

• ED compound has good cytotoxicity results at PC3 cells assays.

• ED compound has a high probability to be safe in humans, validated by web servers of prediction of ADME and toxicity.

Abstract

We investigated compounds selected by molecular docking to identify a specific treatment for COVID-19 that decreases the interaction between angiotensin-converting enzyme 2 (ACE2) and the receptor-binding domain (RBD) of SARS-CoV-2. Five compounds that interact with ACE2 amino acids Gln24, Asp30, His34, Tyr41, Gln42, Met82, Lys353, and Arg357 were evaluated using specific binding assays for their effects on the interaction between ACE2 with RBD. The compound labeled ED demonstrated favorable ACE2-binding, with an IC₅₀ of 31.95 μM. ED cytotoxicity, evaluated using PC3 cells in an MTT assay, was consistent with the low theoretical toxicity previously reported. We propose that ED mainly interacts with His34, Glu37, and Lys353 in ACE2 and that it has an inhibitory effect on the interaction of ACE2 with the RBD of the S-protein. We recommend further investigation to develop ED into a potential drug or adjuvant in COVID-19 treatment.