Potential chimeric peptides to block the SARS-CoV-2 spike receptor-binding domain

Area of Science:

• * Computational biology and bioinformatics
• * Virology
• * Drug discovery

Background:

• * No current vaccines or medicines exist to control the COVID-19 pandemic caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2).
• * Antiviral peptides offer a promising alternative to conventional drugs for combating viral infections, including SARS-CoV-2.
• * The SARS-CoV-2 Spike receptor-binding domain (nCoV-RBD) is crucial for viral attachment and entry via interaction with human angiotensin-converting enzyme 2 (hACE2).

Purpose of the Study:

• * To design and identify novel peptides capable of blocking the interaction between the SARS-CoV-2 nCoV-RBD and hACE2.
• * To investigate the potential of these designed peptides as antiviral agents against SARS-CoV-2.
• * To screen and select the most effective peptides based on binding affinity and antiviral properties.

Main Methods:

• * Employed three distinct bioinformatics strategies to design peptides targeting the nCoV-RBD-hACE2 interface.
• * Identified key interacting amino acid residues on both nCoV-RBD and hACE2.
• * Designed peptides based on hACE2 sequences, screened existing antibacterial peptide databases, and utilized a chimeric peptide design approach.

Main Results:

• * Identified three critical amino acid stretches in hACE2 that interact with nCoV-RBD.
• * Determined that effective peptides must bind to specific key positions on nCoV-RBD, notably Phe486, Gln493, and Asn501.
• * Identified 17 potential peptides, with cnCoVP-4 emerging as the most promising candidate due to its ability to block all three key sites and meet selection criteria.

Conclusions:

• * Successfully identified 17 peptides with potential to inhibit SARS-CoV-2 entry by binding to the nCoV-RBD.
• * Highlighted 10 peptides, including cnCoVP-4, as having significant potential for further experimental validation.
• * The designed peptides represent a potential therapeutic strategy to prevent SARS-CoV-2 infection by blocking viral attachment to host cells.