新型冠状病毒3CL水解酶的结构特征及其抗原表位分析

Analysis of Structural Features and Potential Epitopes in 3C-like Protease(3CL^pro)of SARS-CoV-2

新型冠状病毒(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)含有的3CLpro(3C-like protease)是由306个氨基酸构成的亲水性蛋白酶。3CLpro序列在冠状病毒中高度保守,对SARS-CoV-2的正常功能至关重要。为了深入了解3CL水解酶的结构特征及其抗原表位,本研究利用多种生物信息学软件分析了该酶的理化性质、亲/疏水性、跨膜区、糖基化位点、磷酸化位点、SUMO化位点、二级结构和结构域、配体结合位点及B/T细胞的优势抗原表位,结果发现3CLpro不存在跨膜区,并推测含有糖基化位点2个、磷酸化位点27个、SUMO化位点3个;3CLpro的二级结构以α-螺旋和β-折叠为主,结构域包含一个endopeptidase/C30保守序列;3CLpro存在5个可能的配体结合位点和多个潜在的B/T细胞表位。此外,DrugBank数据库还预测到8个潜在的小分子药物。综上所述,本研究为新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)的药物和疫苗研制提供了理论基础。

The 3C-like protease(3CLpro)of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),containing 306 amino acids,is a hydrophilic protease.Its sequence is highly conserved in coronavirus and is critically important for normal function of SARS-CoV-2.To get insight into 3CLpro structure and antigenic epitope positions,series of bioinformatics databases and software were used,and physicochemical property,hydrophobicity,transmembrane region,glycosylation,phosphorylation and sumoylation sites,secondary structure and structural domains,ligand binding sites and potential B/T cell dominant epitopes of the antigen were analyzed.The results showed that 3CLpro contains zero transmembrane region,2 glycosylation sites,27 phosphorylation sites,3 sumoylation sites.Its secondary structure mainly contains α-helices and β-folds.The structural domains also include one endopeptidase/C30 conserved sequence.Moreover,5 possible ligand binding sites and many epitope regions of B/T cells exist in 3CLpro.Lastly,8 potential small molecule drugs were detected from DrugBank database.This study may provide a theoretical basis for further research on novel drugs and vaccines against coronavirus disease 2019(COVID-19).