TY - JOUR
T1 - Identifying compounds that prevent the binding of the SARS-CoV-2 S-protein to ACE2
AU - Benítez-Cardoza, Claudia Guadalupe
AU - Vique-Sánchez, José Luis
N1 - Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2021/9
Y1 - 2021/9
N2 - 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.
AB - 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.
KW - ACE2
KW - COVID-19
KW - Docking
KW - Inhibitors of ACE2/RBD
KW - SARS-CoV-2
UR - http://www.scopus.com/inward/record.url?scp=85111591965&partnerID=8YFLogxK
U2 - 10.1016/j.compbiomed.2021.104719
DO - 10.1016/j.compbiomed.2021.104719
M3 - Artículo
C2 - 34358993
AN - SCOPUS:85111591965
SN - 0010-4825
VL - 136
JO - Computers in Biology and Medicine
JF - Computers in Biology and Medicine
M1 - 104719
ER -