计算机模拟筛选坛紫菜中新型冠状病毒主蛋白酶抑制肽

Screening for Novel SARS-CoV-2 Main Protease Inhibitory Peptides from Porphyra haitanensis via Computer Simulation

摘要:

新型冠状病毒感染（COVID-19）在我国的疫情流行和病亡数得到控制，但该病毒仍具有感染性和传播性，抑制新冠病毒主蛋白酶（SARS-CoV-2 Mpro）的活性能够降低感染病毒的概率。该研究从坛紫菜蛋白质中筛选出对SARS-CoV-2 Mpro具有抑制作用的多肽。通过文献检索搜集到29种坛紫菜蛋白质，结合其预测的理化性质及潜在致敏性筛选出10种具有代表性的坛紫菜蛋白，对10种坛紫菜蛋白进行模拟胃肠道水解筛选出（2≤肽段长度≤5）肽段后，对坛紫菜源多肽的理化性质进行预测筛选，得到21条亲水、无毒且无潜在致敏性的肽段作为配体，以SARS-CoV-2 Mpro为受体，采用分子对接技术筛选与靶蛋白有较好亲和作用的生物活性肽，通过2D和3D可视化分析生物活性肽与靶蛋白的结合模式及相互作用。结果发现，部分活性肽可进入靶蛋白的活性中心，且通过氢键作用、π键作用以及烷基作用与SARS-CoV-2 Mpro结合。其中，结合分数最高的多肽是DGSF（145.441），其次是DQF（143.819）和DGPW（141.446），表明多肽对SARS-CoV-2 Mpro具有潜在抑制作用。综上所述，坛紫菜蛋白质具备作为后疫情时代营养补充剂的潜力。

Abstract:

While the COVID-19 pandemic and COVID-19-related mortality in China have been under control, SARSCoV-2 remains infectious and transmissible. Inhibiting the activity of SARS-CoV-2 main protease (SARS-CoV-2 Mpro) can reduce viral infectivity. A screen for peptides from Porphyra haitanensis proteins with inhibitory potency toward SARSCoV-2 Mpro was performed, and twenty-nine P. haitanensis proteins identified through a literature search. Ten representative proteins were selected from among them based on predicted physicochemical properties and potential allergenicity. These representative proteins were subsequently subjected to simulated gastrointestinal hydrolysis to screen out the peptides with lengths in the range of 2~5 amino acids. These were subjected to predictive screening based on the physicochemical properties of the peptides of Porphyra haitanensis. Twenty-one hydrophilic and non-toxic peptides with no potential allergenicity were identified and assessed as ligands for the receptor SARS-CoV-2 Mpro. Bioactive peptides with high affinity for the target protein were identified by molecular docking, and the binding modes and interactions between the bioactive peptides and the target protein were analyzed by 2D and 3D visualization. Some of the active peptides entered the active center of the target protein and bound to SARS-CoV-2 Mpro forming hydrogen bonds, π-bonds, and alkyl bonds. The peptide that exhibited the highest bound fraction was DDGSF (145.441), followed by DQF (143.819), and then DGPW (141.446). These studies suggest that peptides have the potential to inhibit SARS-CoV-2 Mpro, and that P. haitanensis proteins thus have potential as nutritional supplements with possible protective efficacy against SARS-CoV-2.