ACE2-derived peptides interact with the RBD domain of SARS-CoV-2 spike glycoprotein, disrupting the interaction with the human ACE2 receptor

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

Keywords:

• SARS-CoV-2 RBD
• COVID-19
• ACE2 receptor
• ACE2-derived peptides

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

Grants from the following Brazilian agencies supported this work: The National Council for Scientific and Technological Development (CNPq), with a doctoral grant to JLA and a research grant (codes 431511/2016-0 and 306202/2017-4) to JTAO; the Office to Coordinate Improvement of University Personnel (CAPES) sponsored PFNS with a postdoctoral fellowship. The authors are also grateful for the support received from the National Center for High-Performance Processing – Federal University of Ceará and Center for Ongoing Education in Health Care-CEATS/School of Public Health of Ceará (ESP-CE).