bioRxiv Science⌕ Search

Biology subjects

Düzgünes, N.

Publications and source records attributed to Düzgünes, N..

2 recordsLinked to original sources

A peptide derived from the SARS-CoV-2 S2-protein heptad-repeat-2 inhibits pseudoviral fusion at micromolar concentrations: Role of palmitic acid conjugation

SARS-CoV-2 S protein-mediated fusion is thought to involve the interaction of the membrane-distal, or N-terminal heptad repeat (NHR) ("HR1") of the cleaved S2 segment of the protein, and the membrane-proximal, or C-terminal heptad repeat (CHR) ("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.

microbiology↗

BROADLY NEUTRALIZING ANTI- HIV-1 ANTIBODIES DO NOT INHIBIT HIV-1 ENV-MEDIATED CELL-CELL FUSION

PG9, PG16, PGT121, and PGT145 antibodies were identified from culture media of activated memory B-cells of an infected donor and shown to neutralize many HIV-1 strains. Since HIV-1 spreads via both free virions and cell-cell fusion, we examined the effect of the antibodies on HIV-1 Env-mediated cell-cell fusion. Clone69TRevEnv cells that express Env in the absence of tetracycline were labeled with Calcein-AM Green, and incubated with CD4+ SupT1 cells labeled with CellTrace Calcein Red-Orange, with or without antibodies. Monoclonal antibodies PG9, PG16, 2G12, PGT121, and PGT145 (at up to 50 g/mL) had little or no inhibitory effect on fusion between HIV-Env and SupT1 cells. By contrast, Hippeastrum hybrid agglutinin completely inhibited fusion. Our results indicate that transmission of the virus or viral genetic material would not be inhibited by these broadly neutralizing antibodies. Thus, antibodies generated by HIV-1 vaccines should be screened for their inhibitory effect on Env-mediated cell-cell fusion.

microbiology↗