Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Molecules. 2020 Dec 24;26(1):57. doi: 10.3390/molecules26010057.
The novel coronavirus disease (2019-nCoV) has been affecting global health since the end of 2019, and there is no sign that the epidemic is abating. Targeting the interaction between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and the human angiotensin-converting enzyme 2 (ACE2) receptor is a promising therapeutic strategy. In this study, surface plasmon resonance (SPR) was used as the primary method to screen a library of 960 compounds. A compound 02B05 (demethylzeylasteral, CAS number: 107316-88-1) that had high affinities for S-RBD and ACE2 was discovered, and binding affinities (K, μM) of 02B05-ACE2 and 02B05-S-RBD were 1.736 and 1.039 μM, respectively. The results of a competition experiment showed that 02B05 could effectively block the binding of S-RBD to ACE2 protein. Furthermore, pseudovirus infection assay revealed that 02B05 could inhibit entry of SARS-CoV-2 pseudovirus into 293T cells to a certain extent at nontoxic concentration. The compoundobtained in this study serve as references for the design of drugs which have potential in the treatment of COVID-19 and can thus accelerate the process of developing effective drugs to treat SARS-CoV-2 infections.
自 2019 年底以来，新型冠状病毒病（2019-nCoV）一直影响着全球健康，没有迹象表明疫情正在减弱。针对严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）刺突蛋白与人类血管紧张素转换酶 2（ACE2）受体之间的相互作用是一种很有前途的治疗策略。在这项研究中，表面等离子体共振（SPR）被用作筛选 960 种化合物库的主要方法。发现了一种对 S-RBD 和 ACE2 具有高亲和力的化合物 02B05（去甲基泽拉司他醇，CAS 号：107316-88-1），其 02B05-ACE2 和 02B05-S-RBD 的结合亲和力（K，μM）分别为 1.736 和 1.039 μM。竞争实验的结果表明，02B05 可以有效阻断 S-RBD 与 ACE2 蛋白的结合。此外，假病毒感染实验表明，02B05 可以在非毒性浓度下在一定程度上抑制 SARS-CoV-2 假病毒进入 293T 细胞。本研究获得的化合物可作为药物设计的参考，这些药物在治疗 COVID-19 方面具有潜力，从而加速开发有效治疗 SARS-CoV-2 感染的药物的进程。
