Ramirez-Acosta Kendra, Rosales-Fuerte Ivan A, Perez-Sanchez J Eduardo, Nuñez-Rivera Alfredo, Juarez Josue, Cadena-Nava Ruben D
Centro de Nanociencias y Nanotecnología - Universidad Nacional Autónoma de México (UNAM) - Ensenada, Baja California, México.
Centro de Investigación Científica y de Educación Superior de Ensenada, Baja California, (CICESE), Ensenada, Baja California, México.
Beilstein J Nanotechnol. 2022 Jul 22;13:699-711. doi: 10.3762/bjnano.13.62. eCollection 2022.
The novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is currently one of the most contagious viruses in existence and the cause of the worst pandemic in this century, COVID-19. SARS-CoV-2 infection begins with the recognition of the cellular receptor angiotensin converting enzyme-2 by its spike glycoprotein receptor-binding domain (RBD). Thus, the use of small peptides to neutralize the infective mechanism of SARS-CoV-2 through the RBD is an interesting strategy. The binding ability of 104 peptides (University of Nebraska Medical Center's Antimicrobial Peptide Database) to the RBD was assessed using molecular docking. Based on the molecular docking results, peptides with great affinity to the RBD were selected. The most common amino acids involved in the recognition of the RBD were identified to design novel peptides based on the number of hydrogen bonds that were formed. At physiological pH, these peptides are almost neutral and soluble in aqueous media. Interestingly, several peptides showed the capability to bind to the active surface area of the RBD of the Wuhan strain, as well as to the RBD of the Delta variant and other SARS-Cov-2 variants. Therefore, these peptides have promising potential in the treatment of the COVID-19 disease caused by different variants of SARS-CoV-2. This research work will be focused on the molecular docking of peptides by molecular dynamics, in addition to an analysis of the possible interaction of these peptides with physiological proteins. This methodology could be extended to design peptides that are active against other viruses.
新型严重急性呼吸综合征冠状病毒2（SARS-CoV-2）是目前存在的传染性最强的病毒之一，也是本世纪最严重的大流行疾病——新冠肺炎的病原体。SARS-CoV-2感染始于其刺突糖蛋白受体结合域（RBD）识别细胞受体血管紧张素转换酶2。因此，利用小肽通过RBD中和SARS-CoV-2的感染机制是一种有趣的策略。使用分子对接评估了104种肽（内布拉斯加大学医学中心抗菌肽数据库）与RBD的结合能力。基于分子对接结果，选择了与RBD具有高亲和力的肽。根据形成的氢键数量，确定了参与RBD识别的最常见氨基酸，以设计新型肽。在生理pH值下，这些肽几乎呈中性，可溶于水性介质。有趣的是，几种肽显示出能够与武汉株RBD的活性表面积结合，也能与Delta变体及其他SARS-CoV-2变体的RBD结合。因此，这些肽在治疗由SARS-CoV-2不同变体引起的新冠肺炎疾病方面具有广阔的潜力。除了分析这些肽与生理蛋白的可能相互作用外，本研究工作将集中于通过分子动力学对肽进行分子对接。这种方法可以扩展到设计对其他病毒有活性的肽。
