Houchi Selma, Messasma Zakia
Department of Biochemistry, Laboratory of Applied Biochemistry, Faculty of Life and Nature Sciences, University of Ferhat Abbas Setif-1, Algeria.
Department of Process Engineering, Laboratory of Electrochemistry, Molecular Engineering and Redox Catalysis, Faculty of Technology, University of Ferhat Abbas Setif-1, 19000, Algeria.
J Mol Struct. 2022 Sep 5;1263:133032. doi: 10.1016/j.molstruc.2022.133032. Epub 2022 Apr 9.
The B.1.617.2 Delta variant is considered to be the most infectious of all SARS-CoV2 variants. Here, an attempt has been made through screening of 55 bioactive compounds from two selected plants, and as potential inhibitors of two viral proteases, main protease Mpro (PDB ID:6LU7) and the RBD of SGP of Sars-CoV-2 B1.617.2 Delta variant (PDB ID:7ORB) where the binding energy, molecular interactions, ADMET/Tox, chemical descriptors and Quantum-Chemical Calculations were explored. Molecular docking results demonstrated that the three top docked compounds formed relatively stable complexes within the active site and displayed remarkable binding energy in the order of Tangshenoside III, Rutin and Hesperidin (-9.35, -9.14 and -8.57 kcal/mol, respectively) with Mpro and Rutin, Tangshenoside III and Hesperidin (-9.07, -7.71 and -7.57 kcal/mol) with RBD of SGP. These compounds are non-Mutagen and non-carcinogen. Therefore, according to the Lipinski's Rule of Five they exhibited three violations concerning hydrogen acceptor, donor and molecular weight. However, based on the Quantum-Chemical Calculations results the selected ligands have effective reactivity, as they showed lower band gaps The difference of the E and E was low, ranging from 0.0639 to 0.0978 a.u, implying the strong affinity of these inhibitors towards the target proteins. Among the three inhibitors, Rutin exhibited higher reactivity against two viral proteases, main protease (Mpro) and the Sars-CoV-2 B1.617.2, as the band energy gap was lowest among all the three phytochemicals, 0.0639 a.u This could indicate that Rutincan be potential anti-viral drug candidates against the existing SARS-CoV-2, the B.1.617.2 Delta variant.
B.1.617.2德尔塔变种被认为是所有新冠病毒变种中传染性最强的。在此，我们尝试从两种选定植物中筛选55种生物活性化合物，作为两种病毒蛋白酶的潜在抑制剂，这两种蛋白酶分别是主要蛋白酶Mpro（蛋白质数据银行编号：6LU7）和新冠病毒B1.617.2德尔塔变种刺突糖蛋白（SGP）的受体结合域（RBD，蛋白质数据银行编号：7ORB），同时探究了它们的结合能、分子相互作用、药物代谢动力学/毒理学性质、化学描述符和量子化学计算。分子对接结果表明，三种对接得分最高的化合物在活性位点内形成了相对稳定的复合物，与Mpro结合时，唐松草苷III、芦丁和橙皮苷的结合能表现出色，分别为-9.35、-9.14和-8.57千卡/摩尔；与SGP的RBD结合时，芦丁、唐松草苷III和橙皮苷的结合能分别为-9.07、-7.71和-7.57千卡/摩尔。这些化合物无致突变性和致癌性。因此，根据Lipinski五规则，它们在氢受体、供体和分子量方面存在三个不符合规则之处。然而，基于量子化学计算结果，所选配体具有有效的反应活性，因为它们显示出较低的带隙。最高占据分子轨道能量（E）和最低未占据分子轨道能量（E）之差较小，在0.0639至0.0978原子单位之间，这意味着这些抑制剂与靶蛋白具有很强的亲和力。在这三种抑制剂中，芦丁对两种病毒蛋白酶，即主要蛋白酶（Mpro）和新冠病毒B1.617.2表现出更高的反应活性，因为其带隙能量在所有三种植物化学物质中最低，为0.0639原子单位。这可能表明芦丁有望成为针对现有新冠病毒B.1.617.2德尔塔变种的抗病毒候选药物。
