Bui Thanh Q, Phuong Loan Huynh Thi, Ai My Tran Thi, Quang Duong Tuan, Phuong Thuy Bui Thi, Nhan Vo Duy, Quy Phan Tu, Van Tat Pham, Dao Duy Quang, Trung Nguyen Tien, Huynh Lam K, Ai Nhung Nguyen Thi
Department of Chemistry, University of Sciences, Hue University Hue City 530000 Vietnam
Department of Chemistry, University of Education, Hue University Hue City 530000 Vietnam.
RSC Adv. 2020 Aug 21;10(51):30961-30974. doi: 10.1039/d0ra05159d. eCollection 2020 Aug 17.
Ribavirin and remdesivir have been preclinically reported as potential drugs for the treatment of SARS-CoV-2 infection, while light silver tetrylene complexes (NHE-AgCl and (NHE-AgCl) with E = C, Si, and Ge) have gained significant interest due to their promising applicability on the cytological scale. Firstly, the structures and bonding states of silver-tetrylene complexes (NHE-Ag) and bis-silver-tetrylene complexes (NHE-Ag-bis) were investigated using density functional theory (DFT) at the BP86 level with the def2-SVP and def2-TZVPP basis sets. Secondly, the inhibitory capabilities of the carbene complexes (NHC-Ag and NHC-Ag-bis) and the two potential drugs (ribavirin and remdesivir) on human-protein ACE2 and SARS-CoV-2 protease PDB6LU7 were evaluated using molecular docking simulation. The carbene ligand NHC bonds in a head-on configuration with AgCl and (AgCl), whereas, the other NHE (E = Si and Ge) tetrylene ligands bond in a side-on mode to the metal fragments. The bond dissociation energy (BDE) of the NHE-Ag bond in the complex families follows the order of NHC-Ag > NHSi-Ag > NHGe-Ag and NHSi-Ag-bis > NHGe-Ag-bis > NHC-Ag-bis. The natural bond orbital analysis implies that the [NHE→AgCl] and [(NHE)→(AgCl)] donations are derived mainly from the σ- and π-contributions of the ligands. The docking results indicate that both the ACE2 and PDB6LU7 proteins are strongly inhibited by silver-carbene NHC-Ag, bis-silver-carbene NHC-Ag-bis, ribavirin, and remdesivir with the docking score energy values varying from -17.5 to -16.5 kcal mol and -16.9 to -16.6 kcal mol, respectively. The root-mean-square deviation values were recorded to be less than 2 Å in all the calculated systems. Thus, the present study suggests that silver-carbene NHC-Ag and bis-silver-carbene NHC-Ag-bis complexes are potential candidates to inhibit ACE2 and PDB6LU7, and thus potentially conducive to prevent infection caused by the SARS-CoV-2 virus.
利巴韦林和瑞德西韦在临床前研究中已被报道为治疗新型冠状病毒肺炎（SARS-CoV-2）感染的潜在药物，而轻量的特屈伦银配合物（NHE-AgCl和（NHE-AgCl），其中E = C、Si和Ge）因其在细胞学尺度上具有广阔的应用前景而备受关注。首先，采用密度泛函理论（DFT）在BP86水平下，使用def2-SVP和def2-TZVPP基组研究了特屈伦银配合物（NHE-Ag）和双特屈伦银配合物（NHE-Ag-bis）的结构和键合状态。其次，利用分子对接模拟评估了卡宾配合物（NHC-Ag和NHC-Ag-bis）以及两种潜在药物（利巴韦林和瑞德西韦）对人类蛋白血管紧张素转换酶2（ACE2）和新型冠状病毒肺炎蛋白酶PDB6LU7的抑制能力。卡宾配体NHC以头对头构型与AgCl和（AgCl）键合，而其他NHE（E = Si和Ge）特屈伦配体以侧对侧模式与金属片段键合。配合物家族中NHE-Ag键的键解离能（BDE）顺序为NHC-Ag > NHSi-Ag > NHGe-Ag以及NHSi-Ag-bis > NHGe-Ag-bis > NHC-Ag-bis。自然键轨道分析表明，[NHE→AgCl]和[(NHE)→(AgCl)]的电子给予主要源于配体的σ和π贡献。对接结果表明，卡宾银NHC-Ag、双卡宾银NHC-Ag-bis、利巴韦林和瑞德西韦均对ACE2和PDB6LU7蛋白有强烈抑制作用，对接分数能量值分别在-17.5至-16.5 kcal/mol和-16.9至-16.6 kcal/mol之间。在所有计算体系中，均记录到均方根偏差值小于2 Å。因此，本研究表明卡宾银NHC-Ag和双卡宾银NHC-Ag-bis配合物是抑制ACE2和PDB6LU7的潜在候选物，因此可能有助于预防新型冠状病毒肺炎病毒引起的感染。
