Design of Entry Inhibitor Peptides Covalently Bonding SARS-CoV-2 Variants in Wastewater

Area of Science:

• Biochemistry
• Virology
• Materials Science

Background:

• The COVID-19 pandemic necessitates universal inhibitors against SARS-CoV-2 variants.
• Protein-protein interactions between the SARS-CoV-2 receptor-binding domain (RBD) and human angiotensin-converting enzyme 2 (hACE2) are critical for viral entry.
• Mutations in the RBD can lead to immune escape and reduced inhibitor efficacy.

Purpose of the Study:

• To design and develop novel entry inhibitor peptides with broad activity against SARS-CoV-2 variants.
• To create a peptide-based system for capturing and enriching SARS-CoV-2 pseudovirus from environmental water samples.

Main Methods:

• In silico screening identified affinity peptides by analyzing hot spot residues of hACE2 interacting with the prototype RBD.
• Peptides were modified with sulfur(VI) fluoride exchange reaction and a PEG12 spacer arm for irreversible binding to RBD.
• Modified peptides were conjugated with magnetic beads for preconcentration of SARS-CoV-2 pseudovirus.

Main Results:

• The modified peptides formed irreversible bonds with a wide range of RBD, potentially overcoming variant escape.
• The peptide-magnetic bead system achieved 15-75% recovery rates for SARS-CoV-2 pseudovirus in wastewater samples.
• Effective preconcentration was demonstrated across a concentration range of 10²-10⁷ copies/mL.

Conclusions:

• The designed entry inhibitor peptides offer a promising strategy for broad-spectrum SARS-CoV-2 inhibition.
• These peptides can be utilized for developing advanced viral capturing, enrichment, and detection technologies.
• The findings contribute to environmental monitoring strategies for viral pathogens.