Researchers identify a conserved site on SARS-CoV-2 spike that a broadly neutralizing macrocyclic peptide can target biorxivpreprint UniUtrecht ANUmedia Sydney_Uni SARSCoV2 spike coronavirus covid COVID19 peptide
By Bhavana KunkalikarNov 17 2022Reviewed by Danielle Ellis, B.Sc. In a recent study posted to the bioRxiv* preprint server, researchers explored the efficiency of a macrocyclic peptide in inhibiting the severe acute respiratory syndrome coronavirus 2 spike protein.
The team assembled two peptide libraries containing nearly 1012 distinct sequences using the random non-standard peptide integrated discovery technique. During translation, peptides are tagged with their encoding messenger ribonucleic acid and cyclized by recoding methionine into N-chloroacetylated L-tyrosine or D-tyrosine, which can cyclize with a cysteine residue present after 15 random codons encoding any of the remaining 19 L-amino acids.
Furthermore, high throughput next-generation sequencing was performed for all the enriched libraries. This led to the detection of sequences that were subsequently counted, aligned, and clustered based on sequence similarity to select 15 possible cyclic peptide ligands by solid-phase peptide synthesis. The activity of 10 purified synthetic cyclic peptides was then evaluated in a pseudovirus assay performed for the detection of the SARS-CoV-2 WT strain.
An enzyme-linked immunosorbent test determined that none of the active peptides blocked spike binding to ACE2, indicating that both may be binding to an auxiliary location. The peptide S1b3inL1 demonstrated good efficacy with a half maximal effective concentration of 5.8 M, whereas the analogous peptide S1b3inL4 exhibited less potent neutralization of the virus.
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