ABSTRACT
SARS-CoV-2 S protein-mediated fusion is thought to involve the interaction of the membrane-distal, or N-terminal heptad repeat (NHR) (termed HR1) of the cleaved S2 segment of the protein, and the membrane-proximal, or C-terminal heptad repeat (CHR) (termed HR2) regions of the protein. Following the observations of Xia et al (Xia S, Liu M, Wang C, Xu W, Lan Q, Feng S, Qi F, Bao L, Du L, Liu S, Qin C, Sun F, Shi Z, Zhu Y, Jiang S, Lu L. Cell Res. 2020b Apr;30(4):343-355), we examined the fusion inhibitory activity of a PEGylated HR2-derived peptide and its palmitoylated derivative, using a pseudovirus infection assay. The latter peptide caused a 76% reduction in fusion activity at 10 M. Our results suggest that small variations in peptide derivatization and differences in the membrane composition of pseudovirus preparations may affect the inhibitory potency of HR2-derived peptides.