Laboratorio de Investigación Bioquímica, ENMyH-Instituto Politécnico Nacional, Ciudad de México, Mexico.
Facultad de Medicina Mexicali, Universidad Autónoma de Baja California, Mexicali, BC, Mexico; Ciencias de La Salud Mexicali, Universidad Autónoma de Baja California, Mexicali, BC, Mexico.
Comput Biol Med. 2021 Sep;136:104719. doi: 10.1016/j.compbiomed.2021.104719. Epub 2021 Jul 31.
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 IC 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.
我们研究了通过分子对接选择的化合物，以确定针对 COVID-19 的特定治疗方法，该方法可减少血管紧张素转换酶 2（ACE2）与 SARS-CoV-2 的受体结合域（RBD）之间的相互作用。使用特定的结合测定法评估了与 ACE2 氨基酸 Gln24、Asp30、His34、Tyr41、Gln42、Met82、Lys353 和 Arg357 相互作用的五种化合物对 ACE2 与 RBD 之间相互作用的影响。用 ED 标记的化合物表现出对 ACE2 的有利结合，IC 为 31.95 μM。用 MTT 测定法在 PC3 细胞中评估 ED 的细胞毒性与先前报道的低理论毒性一致。我们提出 ED 主要与 ACE2 中的 His34、Glu37 和 Lys353 相互作用，并且对 ACE2 与 S 蛋白的 RBD 的相互作用具有抑制作用。我们建议进一步研究，将 ED 开发为 COVID-19 治疗的潜在药物或佐剂。
