Recent COVID-19 outbreak has prompted the search of novel therapeutic agents to treat the disease. The initial step of the infection involves the binding of the virus through the viral spike protein with the host angiotensin converting enzyme 2 (ACE2). In this study, the interaction of some ACE or ACE2 inhibitors and their analogues as well as selected compounds with the viral spike protein as a strategy to hinder viral-ACE2 interaction were investigated. SARS-CoV-2 spike protein as well as the ligands were retrieved from protein databank and ChEBI database respectively. The molecules were prepared before initiating the virtual screening using PyRx software. Discovery studio was used to further visualize the binding interactions between the compounds and the protein. The ACE inhibitors and their analogues fosinopril (1-), fosinopril and moexipril have the best binding affinity to the protein with binding energies < − 7.0 kcal/mol while non-flavonoid stilben-4-ol binds with free binding energy of − 7.1 kcal/mol. Others compounds which belong to either the flavonoids, terpenes and alkaloid classes also have binding energies < − 7.0 kcal/mol. Such high binding energies were enhanced via hydrogen bond (h-bond) interactions in addition to other interactions observed between the compounds and the amino acid residues of the protein. The ACE inhibitors and their analogues as well as the selected compounds could serve as inhibitors of the spike protein as well as lead in drug discovery processes to target the SARS-CoV-2 virus.

中文翻译：

---

SARS-CoV-2 刺突蛋白与血管紧张素转换酶抑制剂以及从具有生物学意义的化学实体中选择的化合物的相互作用

最近的 COVID-19 爆发促使人们寻找新的治疗药物来治疗该疾病。感染的第一步涉及病毒通过病毒刺突蛋白与宿主血管紧张素转换酶 2 (ACE2) 结合。在这项研究中，研究了一些 ACE 或 ACE2 抑制剂及其类似物以及选定的化合物与病毒刺突蛋白的相互作用，作为阻碍病毒-ACE2 相互作用的策略。SARS-CoV-2刺突蛋白及其配体分别从蛋白质数据库和ChEBI数据库中检索。在使用 PyRx 软件开始虚拟筛选之前准备好分子。Discovery studio 用于进一步可视化化合物与蛋白质之间的结合相互作用。ACE 抑制剂及其类似物 fosinopril (1-)、fosinopril 和 moexipril 对蛋白质具有最佳结合亲和力，结合能 < − 7.0 kcal/mol，而非类黄酮 stilben-4-ol 的自由结合能为 − 7.1 kcal /摩尔。属于类黄酮、萜烯和生物碱类的其他化合物也具有 < - 7.0 kcal/mol 的结合能。除了在化合物和蛋白质的氨基酸残基之间观察到的其他相互作用之外，这种高结合能还通过氢键（h-键）相互作用得到增强。ACE 抑制剂及其类似物以及选定的化合物可以作为刺突蛋白的抑制剂，并引领针对 SARS-CoV-2 病毒的药物发现过程。