Department of Biochemistry and Molecular Biology, Federal University of Ceará, Fortaleza, Brazil.
Department of Physics, Federal University of Ceará, Fortaleza, Brazil.
J Biomol Struct Dyn. 2022 Aug;40(12):5493-5506. doi: 10.1080/07391102.2020.1871415. Epub 2021 Jan 10.
Vaccines could be the solution to the current SARS-CoV-2 outbreak. However, some studies have shown that the immunological memory only lasts three months. Thus, it is imperative to develop pharmacological treatments to cope with COVID-19. Here, the approach by molecular docking, dynamic simulations and quantum biochemistry revealed that ACE2-derived peptides strongly interact with the SARS-CoV-2 RBD domain of spike glycoprotein (S-RBD). ACE2-Dev-PepI, ACE2-Dev-PepII, ACE2-Dev-PepIII and ACE2-Dev-PepIV complexed with S-RBD provoked alterations in the 3D structure of S-RBD, leading to disruption of the correct interaction with the ACE2 receptor, a pivotal step for SARS-CoV-2 infection. This wrong interaction between S-RBD and ACE2 could inhibit the entry of SARS-CoV-2 in cells, and thus virus replication and the establishment of COVID-19 disease. Therefore, we suggest that ACE2-derived peptides can interfere with recognition of ACE2 in human cells by SARS-CoV-2 . Bioinformatic prediction showed that these peptides have no toxicity or allergenic potential. By using ACE2-derived peptides against SARS-CoV-2, this study points to opportunities for further research on these peptides, seeking to discover new drugs and entirely new perspectives to treat COVID-19.Communicated by Ramaswamy H. Sarma.
疫苗可能是解决当前 SARS-CoV-2 爆发的方法。然而，一些研究表明，免疫记忆只能持续三个月。因此，开发药物治疗方法来应对 COVID-19 迫在眉睫。在这里，通过分子对接、动态模拟和量子生物化学的方法揭示了 ACE2 衍生肽与刺突糖蛋白（S-RBD）的 SARS-CoV-2 RBD 结构域强烈相互作用。ACE2-Dev-PepI、ACE2-Dev-PepII、ACE2-Dev-PepIII 和 ACE2-Dev-PepIV 与 S-RBD 复合物引起 S-RBD 三维结构的改变，导致与 ACE2 受体的正确相互作用中断，这是 SARS-CoV-2 感染的关键步骤。S-RBD 和 ACE2 之间的这种错误相互作用可以抑制 SARS-CoV-2 进入细胞，从而抑制病毒复制和 COVID-19 疾病的建立。因此，我们建议 ACE2 衍生肽可以干扰 SARS-CoV-2 对人细胞中 ACE2 的识别。生物信息学预测表明这些肽没有毒性或致敏潜力。通过使用 ACE2 衍生肽来对抗 SARS-CoV-2，本研究为进一步研究这些肽提供了机会，旨在发现治疗 COVID-19 的新药物和全新视角。由 Ramaswamy H. Sarma 交流。
