Harnkit Nathaphat, Khongsonthi Thanakamol, Masuwan Noprada, Prasartkul Pornpinit, Noikaew Tipanart, Chumnanpuen Pramote
Medicinal Plant Research Institute, Department of Medical Sciences, Ministry of Public Health, Nonthaburi 11000, Thailand.
Mahidol Wittayanusorn School, 364 Salaya, Phuttamonthon District, Nakhon Prathom 73170, Thailand.
Antibiotics (Basel). 2022 Sep 27;11(10):1318. doi: 10.3390/antibiotics11101318.
The Coronavirus Disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the loss of life and has affected the life quality, economy, and lifestyle. The SARS-CoV-2 main protease (Mpro), which hydrolyzes the polyprotein, is an interesting antiviral target to inhibit the spreading mechanism of COVID-19. Through predictive digestion, the peptidomes of the four major proteins in rice bran, albumin, glutelin, globulin, and prolamin, with three protease enzymes (pepsin, trypsin, and chymotrypsin), the putative hydrolyzed peptidome was established and used as the input dataset. Then, the prediction of the antiviral peptides (AVPs) was performed by online bioinformatics tools, i.e., AVPpred, Meta-iAVP, AMPfun, and ENNAVIA programs. The amino acid composition and cytotoxicity of candidate AVPs were analyzed by COPid and ToxinPred, respectively. The ten top-ranked antiviral peptides were selected and docked to the SARS-CoV-2 main protease using GalaxyPepDock. Only the top docking scored candidate (AVP4) was further analyzed by molecular dynamics simulation for one nanosecond. According to the bioinformatic analysis results, the candidate SARS-CoV-2 main protease inhibitory peptides were 7-33 amino acid residues and formed hydrogen bonds at Thr22-24, Glu154, and Thr178 in domain 2 with short bonding distances. In addition, these top-ten candidate bioactive peptides contain hydrophilic amino acid residues and have a positive net charge. We hope that this study will provide a potential starting point for peptide-based therapeutic agents against COVID-19.
由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起的2019冠状病毒病（COVID-19）已导致生命损失，并影响了生活质量、经济和生活方式。SARS-CoV-2主要蛋白酶（Mpro）可水解多蛋白，是抑制COVID-19传播机制的一个有趣的抗病毒靶点。通过预测性消化，利用三种蛋白酶（胃蛋白酶、胰蛋白酶和胰凝乳蛋白酶）对米糠中的四种主要蛋白质（白蛋白、谷蛋白、球蛋白和醇溶蛋白）的肽组进行分析，建立了假定的水解肽组并将其用作输入数据集。然后，通过在线生物信息学工具，即AVPpred、Meta-iAVP、AMPfun和ENNAVIA程序，对抗病毒肽（AVP）进行预测。分别通过COPid和ToxinPred分析候选AVP的氨基酸组成和细胞毒性。选择排名前十的抗病毒肽，并使用GalaxyPepDock将其与SARS-CoV-2主要蛋白酶对接。仅对对接得分最高的候选肽（AVP4）进行了一纳秒的分子动力学模拟进一步分析。根据生物信息学分析结果，候选的SARS-CoV-2主要蛋白酶抑制肽为7至33个氨基酸残基，在结构域2的Thr22-24、Glu154和Thr178处形成氢键，键距较短。此外，这十种候选生物活性肽含有亲水性氨基酸残基且净电荷为正。我们希望这项研究将为基于肽的COVID-19治疗药物提供一个潜在的起点。
