Aminu Suleiman, Ibrahim Mohammed Auwal, Sallau Abdullahi Balarabe
Department of Biochemistry, Ahmadu Bello University, Zaria, Nigeria.
Beni Suef Univ J Basic Appl Sci. 2021;10(1):48. doi: 10.1186/s43088-021-00138-3. Epub 2021 Aug 25.
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. 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 virus.
近期的新型冠状病毒肺炎（COVID-19）疫情促使人们寻找治疗该疾病的新型治疗药物。感染的初始步骤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。在本研究中，研究了一些ACE或ACE2抑制剂及其类似物以及选定化合物与病毒刺突蛋白的相互作用，以此作为阻碍病毒与ACE2相互作用的策略。刺突蛋白和配体分别从蛋白质数据库和ChEBI数据库中检索。在使用PyRx软件启动虚拟筛选之前，先对分子进行了制备。使用Discovery studio进一步可视化化合物与蛋白质之间的结合相互作用。
ACE抑制剂及其类似物福辛普利（1-）、福辛普利和莫昔普利与该蛋白质具有最佳结合亲和力，结合能< -7.0 kcal/mol，而非黄酮类芪-4-醇的自由结合能为-7.1 kcal/mol。其他属于黄酮类、萜类和生物碱类的化合物的结合能也< -7.0 kcal/mol。除了观察到的化合物与蛋白质氨基酸残基之间的其他相互作用外，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作为刺突蛋白的抑制剂，并在针对该病毒的药物发现过程中发挥引领作用。
