兼具糖尿病的新型冠状病毒肺炎（Corona Virus Disease 2019，COVID-19）患者病死率明显偏高，抑制Ⅱ型糖尿病关键酶二肽基肽酶4（DPP-IV）和新冠肺炎病毒主蛋白酶（SARS-CoV-2 Mpro）的活性能缓解相应的病症。该研究采用UniProt、NCBI和PDB数据库检索纳豆蛋白，基于BIOPBP-UWM数据库开展计算机模拟胃肠道蛋白酶（胃蛋白酶、胰蛋白酶和胰凝乳蛋白酶）水解纳豆蛋白的研究，最后利用分子对接技术分别研究纳豆蛋白源多肽与DPP-IV和SARS-CoV-2 Mpro的结合能力，分析参与相互作用的氨基酸残基与分子作用力类型。结果发现，糖转运蛋白与两种酶具有良好的结合效果。特别地，序列为ISQPR、TIPVR和STVTR的多肽对两种酶都具有较高的结合分数（≤-130），被鉴定为DPP-IV和SARS-CoV-2 Mpro的双重抑制肽。因此，纳豆蛋白具有缓解Ⅱ型糖尿病病症和作为新型冠状病毒感染病人营养补充剂的潜力。

People with diabetes have a significantly higher mortality rate of coronavirus disease 2019 (COVID-19) than the general population, and the symptoms can be alleviated by inhibiting the activity of the key enzyme of type 2 diabetes, dipeptidyl peptidase-4 (DPP-IV), which is the main protease of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 Mpro). The UniProt, NCBI, and PDB databases were used to search the natto protein. Based on the BIOPBP-UWM database, a computer simulation of the hydrolysis of natto proteins by gastrointestinal proteases (pepsin, trypsin, and chymotrypsin) was conducted. Finally, molecular docking technology was used to study the ability of natto-protein-derived polypeptides to bind to DPP-IV and SARS-CoV-2 Mpro, and the amino acid residues involved in the interaction and the type of molecular forces were analyzed. The sugar transporters were found to strongly bind with the two enzymes. In particular, peptides with the sequences ISQPR, TIPVR, and STVTR had high binding scores (≤-130) for both enzymes and, therefore, were identified as inhibitory peptides of both DPP-IV and SARS-CoV-2 Mpro. Thus, natto protein has the potential to alleviate the symptoms of type 2 diabetes and be used as a nutritional supplement for people infected with COVID-19.

广东省科技创新战略专项资金（2022B1212010015）；广东省基础与应用基础研究基金（2020A1515110326）；广东省市场监督管理局科研攻关项目（2022CS01）；广东省教育厅特色创新项目（2022KTSCX120）