Abstract

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 in silico 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 in vivo. 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 in vivo research on these peptides, seeking to discover new drugs and entirely new perspectives to treat COVID-19.

Communicated by Ramaswamy H. Sarma

摘要

疫苗可能是当前SARS-CoV-2爆发的解决方案。但是，一些研究表明免疫记忆仅持续三个月。因此，必须开发药物治疗以应对COVID-19。在这里，计算机通过分子对接，动态模拟和量子生物化学的方法揭示，ACE2衍生的肽与穗糖蛋白（S-RBD）的SARS-CoV-2 RBD结构域强烈相互作用。与S-RBD复合的ACE2-Dev-PepI，ACE2-Dev-PepII，ACE2-Dev-PepIII和ACE2-Dev-PepIV引起S-RBD的3D结构改变，从而导致与ACE2受体的正确相互作用遭到破坏。 ，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能会抑制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衍生的肽可能干扰SARS-CoV-2在体内对人细胞中ACE2的识别。生物信息学预测表明，这些肽没有毒性或致敏性。通过使用针对SARS-CoV-2的ACE2衍生肽，本研究为这些肽的进一步体内研究提供了机会，以寻求发现新药和治疗COVID-19的全新观点。

由Ramaswamy H.Sarma沟通