Forcelloni Sergio, Benedetti Anna, Dilucca Maddalena, Giansanti Andrea
Mechanisms of Protein Biogenesis, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
Sapienza University of Rome, Department of Physics, P.le A. Moro 5, 00185 Rome, Italy.
Curr Genomics. 2021 Dec 31;22(7):541-549. doi: 10.2174/1389202923666211216162605.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel virus that first occurred in Wuhan in December 2019. The spike glycoproteins and nucleocapsid proteins are the most common targets for the development of vaccines and antiviral drugs.
We herein analyze the rate of evolution along with the sequences of spike and nucleocapsid proteins in relation to the spatial locations of their epitopes, previously suggested to contribute to the immune response caused by SARS-CoV-2 infections.
We compare homologous proteins of seven human coronaviruses: HCoV-229E, HCoV-OC43, SARS-CoV, HCoV-NL63, HCoV-HKU1, MERS-CoV, and SARS-CoV-2. We then focus on the local, structural order-disorder propensity of the protein regions where the SARS-CoV-2 epitopes are located.
We show that most of nucleocapsid protein epitopes overlap the RNA-binding and dimerization domains, and some of them are characterized by a low rate of evolutions. Similarly, spike protein epitopes are preferentially located in regions that are predicted to be ordered and well- conserved, in correspondence of the heptad repeats 1 and 2. Interestingly, both the receptor-binding motif to ACE2 and the fusion peptide of spike protein are characterized by a high rate of evolution.
Our results provide evidence for conserved epitopes that might help develop broad-spectrum SARS-CoV-2 vaccines.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）是一种于2019年12月首次出现在武汉的新型病毒。刺突糖蛋白和核衣壳蛋白是疫苗和抗病毒药物研发中最常见的靶点。
我们在此分析刺突蛋白和核衣壳蛋白序列的进化速率及其与表位空间位置的关系，此前有研究表明这些表位有助于引发由SARS-CoV-2感染引起的免疫反应。
我们比较了七种人类冠状病毒的同源蛋白：HCoV-229E、HCoV-OC43、SARS-CoV、HCoV-NL63、HCoV-HKU1、MERS-CoV和SARS-CoV-2。然后我们重点关注SARS-CoV-2表位所在蛋白质区域的局部结构有序-无序倾向。
我们发现，大多数核衣壳蛋白表位与RNA结合域和二聚化域重叠，其中一些表位的进化速率较低。同样，刺突蛋白表位优先位于预测为有序且保守的区域，对应于七肽重复序列1和2。有趣的是，刺突蛋白与ACE2的受体结合基序和融合肽的进化速率都很高。
我们的结果为保守表位提供了证据，这些表位可能有助于开发广谱SARS-CoV-2疫苗。
