Laboratorio de Investigación Bioquímica, ENMyH-Instituto Politécnico Nacional, Ciudad de México, Mexico.
Facultad de Medicina, Universidad Autónoma de Baja California, Mexicali, BC, Mexico.
Life Sci. 2020 Sep 1;256:117970. doi: 10.1016/j.lfs.2020.117970. Epub 2020 Jun 15.
The COVID-19 disease caused by the SARS-CoV-2 has become a pandemic and there are no effective treatments that reduce the contagion. It is urgent to propose new treatment options, which are more effective in the interaction between viruses and cells. In this study was to develop a search for new pharmacological compounds against the angiotensin-converting enzyme 2 (ACE2), to inhibit the interaction with SARS-CoV-2.
Docking, virtual screening using almost 500,000 compounds directed to interact in the region between the residues (Gln24, Asp30, His34, Tyr41, Gln42, Met82, Lys353, and Arg357) in ACE2. The average of ΔG, the standard deviation value and the theoretical toxicity from compounds were analyzed.
20 best compounds directed to interact in ACE2 with a high probability to be safe in humans, validated by web servers of prediction of ADME and toxicity (ProTox-II and PreADMET), to difficult the interaction between ACE2 and region binding domain (RBD) of SARS-CoV-2.
In this study, 20 compounds were determined by docking focused on the region of interaction between ACE2 and RBD of SARS-CoV-2 was carried out. The compounds are publicly available to validate the effect in in vitro tests.
由 SARS-CoV-2 引起的 COVID-19 疾病已成为大流行，目前尚无减少传染的有效治疗方法。急需提出新的治疗方案，以提高病毒与细胞之间的相互作用的有效性。本研究旨在寻找针对血管紧张素转换酶 2（ACE2）的新型药理学化合物，以抑制其与 SARS-CoV-2 的相互作用。
使用将近 500,000 种化合物对接，进行虚拟筛选，以与 ACE2 中残基（Gln24、Asp30、His34、Tyr41、Gln42、Met82、Lys353 和 Arg357）之间的区域相互作用。分析了化合物的平均ΔG、标准偏差值和理论毒性。
通过对接验证，确定了 20 种最有可能与 ACE2 相互作用且对人类安全的化合物，这些化合物通过 ADME 和毒性预测网络服务器（ProTox-II 和 PreADMET）验证，以阻碍 ACE2 与 SARS-CoV-2 的结合域（RBD）之间的相互作用。
在这项研究中，通过对接确定了 20 种化合物，重点研究 ACE2 与 SARS-CoV-2 的 RBD 相互作用区域。这些化合物可供公开验证其在体外试验中的效果。
