Computational Mutagenesis at the SARS-CoV-2 Spike Protein/Angiotensin-Converting Enzyme 2 Binding Interface: Comparison with Experimental Evidence.
Computational Mutagenesis at the SARS-CoV-2 Spike Protein/Angiotensin-Converting Enzyme 2 Binding Interface: Comparison with Experimental Evidence.
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SARS-CoV-2刺突蛋白/血管紧张素转换酶2结合界面的计算突变：与实验证据的比较。
DOI：
10.1021/acsnano.0c10833
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发表时间：
2021-04-27
期刊：
影响因子：
17.1
通讯作者：
Pricl S
中科院分区：
文献类型：
--
作者：
Laurini E;Marson D;Aulic S;Fermeglia A;Pricl S
由病原体严重急性呼吸道综合征冠状病毒2型（SARS-CoV-2）引起的2019年冠状病毒病（COVID-19）大流行于2019年底在中国开始，并迅速蔓延至全球。自COVID-19出现以来，许多治疗方案一直在不懈地探索，尽管两种疫苗刚刚获得不同政府机构的紧急使用授权，但基于中和抗体和小药物抑制剂的抗病毒治疗仍然是预防和治疗SARS-CoV-2感染的重要可行选择。病毒刺突糖蛋白（S蛋白）是通过识别和结合血管紧张素转换酶2基因（ACE 2）促进人类宿主细胞侵袭的关键分子。在这项工作中，我们报告了通过计算机突变的18个ACE 2残基和14个S-蛋白受体结合域（S-RBDCoV-2）的残基，有助于受体/病毒蛋白结合界面的结果。具体而言，每个野生型蛋白质-蛋白质界面残基分别被疏水性（异亮氨酸）、极性（丝氨酸和苏氨酸）、带电（天冬氨酸/谷氨酸和赖氨酸/精氨酸）和大体积（色氨酸）残基取代，以研究突变氨基酸的性质、形状和尺寸对所得结合界面的结构和强度产生的不同影响。计算结果随后对相应的实验数据进行了后验验证，总体一致率为92%。有趣的是，预测不可忽略数量的错义变异会增强ACE 2/S-RBDCoV-2结合，包括ACE 2上的变体Q24 T、T27 D/K/W、D30 E、H34 S7 T/K、E35 D、Q42 K、L79 I/W、R357 K和R393 K以及S-RBDCoV-2上的L455 D/W、F456 K/W、Q493 K、N501 T和Y505 W。
The coronavirus disease-2019 (COVID-19) pandemic, caused by the pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), started in China during late 2019 and swiftly spread worldwide. Since COVID-19 emergence, many therapeutic regimens have been relentlessly explored, and although two vaccines have just received emergency use authorization by different governmental agencies, antiviral therapeutics based neutralizing antibodies and small-drug inhibitors can still be vital viable options to prevent and treat SARS-CoV-2 infections. The viral spike glycoprotein (S-protein) is the key molecular player that promotes human host cellular invasion via recognition of and binding to the angiotensin-converting enzyme 2 gene (ACE2). In this work, we report the results obtained by mutating in silico the 18 ACE2 residues and the 14 S-protein receptor binding domain (S-RBDCoV-2) residues that contribute to the receptor/viral protein binding interface. Specifically, each wild-type protein–protein interface residue was replaced by a hydrophobic (isoleucine), polar (serine and threonine), charged (aspartic acid/glutamic acid and lysine/arginine), and bulky (tryptophan) residue, respectively, in order to study the different effects exerted by nature, shape, and dimensions of the mutant amino acids on the structure and strength of the resulting binding interface. The computational results were next validated a posteriori against the corresponding experimental data, yielding an overall agreement of 92%. Interestingly, a non-negligible number of mis-sense variations were predicted to enhance ACE2/S-RBDCoV-2 binding, including the variants Q24T, T27D/K/W, D30E, H34S7T/K, E35D, Q42K, L79I/W, R357K, and R393K on ACE2 and L455D/W, F456K/W, Q493K, N501T, and Y505W on S-RBDCoV-2, respectively.
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影响因子：
64.8
作者：
Li W;Moore MJ;Vasilieva N;Sui J;Wong SK;Berne MA;Somasundaran M;Sullivan JL;Luzuriaga K;Greenough TC;Choe H;Farzan M
通讯作者：
Farzan M
影响因子：
5.2
作者：
Benetti, Elisa;Tita, Rossella;Pinto, Anna Maria
通讯作者：
Pinto, Anna Maria
DOI：
10.1126/science.abc0870
发表时间：
2020-09-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Chan KK;Dorosky D;Sharma P;Abbasi SA;Dye JM;Kranz DM;Herbert AS;Procko E
通讯作者：
Procko E
影响因子：
13.6
作者：
Di Giorgio, Salvatore;Martignano, Filippo;Conticello, Silvestro G.
通讯作者：
Conticello, Silvestro G.
影响因子：
2.9
作者：
Kim WY;Hong SB
通讯作者：
Hong SB