A Collection of Designed Peptides to Target SARS-CoV-2 Spike RBD—ACE2 Interaction

Abstract

The angiotensin-converting enzyme 2 (ACE2) is the receptor used by SARS-CoV and SARS-CoV-2 coronaviruses to attach to cells via the receptor-binding domain (RBD) of their viral spike protein. Since the start of the COVID-19 pandemic, several structures of protein complexes involving ACE2 and RBD as well as monoclonal antibodies and nanobodies have become available. We have leveraged the structural data to design peptides to target the interaction between the RBD of SARS-CoV-2 and ACE2 and SARS-CoV and ACE2, as contrasting exemplar, as well as the dimerization surface of ACE2 monomers. The peptides were modelled using our original method: PiPreD that uses native elements of the interaction between the targeted protein and cognate partner(s) that are subsequently included in the designed peptides. These peptides recapitulate stretches of residues present in the native interface plus novel and highly diverse conformations surrogating key interactions at the interface. To facilitate the access to this information we have created a freely available and dedicated web-based repository, PepI-Covid19 database, providing convenient access to this wealth of information to the scientific community with the view of maximizing its potential impact in the development of novel therapeutic and diagnostic agents.

Inhibition of SARS-CoV-2 pathogenesis by potent peptides designed by the mutation of ACE2 binding region

“…Several studies introduced peptide inhibitors against RBD. However, they used different approaches to design peptides [ [54] , [55] , [56] , [57] , [58] , [59] , [60] ], and therefore, their results may seem incomparable to the present study. In the next step, 11 peptides having the greatest OSPREY scores were chosen and their probable allergenicity and toxicity were evaluated.…”

Applying the digital data and the bioinformatics tools in SARS-CoV-2 research

“…For the interaction between the RBD in the spike protein and the host receptor (ACE2) is critical in the invasion of virus, both the Peptide Inhibition Covid 19 Repository [105] and the SARS-CoV-2 Interactome 3D [106] visualize the interaction between RDB and ACE2, facilitating further exploration of this mechanism. Mutations present on the spike protein are likely relevant to viral adaptation and immune escape, SpikePro enables a rapid prediction of the adaptation of some mutant based on the structural models [107] .…”

Bioactive Peptides in Human Health and Disease

“…In their article, Fernandez-Fuentes et al [ 4 ] designed, by a computational approach, a set of peptides able to target the SARS-CoV-2 spike receptor binding domain-ACE2 interface. These peptides may potentially limit the interaction between SARS-CoV-2 spike protein and its receptor on the cell surface (ACE2), decreasing the ability of the virus to infect cells.…”