Design of Three Residues Peptides against SARS-CoV-2 Infection

Area of Science:

• Virology
• Drug Discovery
• Biochemistry

Background:

• The COVID-19 pandemic necessitates novel therapeutic and prophylactic strategies.
• Peptide inhibitors offer a low-toxicity, high-efficiency approach for viral infections.
• Specific nucleotide signatures in Coronaviridae and other pathogens suggest potential therapeutic targets.

Purpose of the Study:

• To investigate the antiviral effects of synthetic peptides derived from identified nucleotide signatures.
• To evaluate the efficacy of these peptides against human coronaviruses HCoV-OC43 and SARS-CoV-2.
• To determine the mechanism of action and safety profile of the candidate peptides.

Main Methods:

• Synthesis of peptides based on identified nucleotide signatures.
• In vitro testing of peptide efficacy against HCoV-OC43 and SARS-CoV-2 infection.
• Molecular docking simulations to predict peptide-Spike protein binding.
• Biochemical assays to validate binding and assess peptide stability and toxicity.

Main Results:

• Synthetic peptides demonstrated dose-dependent inhibition of both HCoV-OC43 and SARS-CoV-2 infection.
• Peptides bind to the Receptor Binding Domain (RBD) of the Spike protein, as confirmed by molecular docking and biochemical studies.
• Tested peptides exhibited no toxicity to cultured cells or human erythrocytes.
• The peptides proved resistant to degradation by human serum proteases.

Conclusions:

• The studied synthetic peptides are effective inhibitors of HCoV-OC43 and SARS-CoV-2.
• These peptides function by targeting the Spike protein's RBD.
• The peptides possess favorable safety and stability profiles, indicating significant potential as antiviral agents.