A boost to the antiviral activity

A boost to the antiviral activity

July 14, 2020 news 0

New paper “A boost to the antiviral activity: Cholesterol tagged peptides derived from glycoprotein B of Herpes Simplex virus type I” published in International Journal of Biological Macromolecules


Conformational changes of viral glycoproteins govern the fusion of viral and cellular membranes in the entry of enveloped viruses. Peptides mimicking domains of viral glycoproteins are apt to interfere with the fusion event, likely hampering the conformational rearrangements from the pre- to the post-fusion structures. We previously developed a peptide sequence with a high potential to inhibit the entry of herpes simplex type 1, which was able to trap glycoprotein B at an intermediate stage, arresting fusion. We propose that similarly to other viruses, membrane targeting through cholesterol conjugation may potently block fusion. The peptide conjugated to polyethylenglycol and cholesterol interacts with viral and cell membranes thanks to the presence of cholesterol and blocks the conformational rearrangements of the glycoprotein B. Here, we also probed the effect of the linker (polyethylenglycol) length on the activity. By targeting the peptide gBh1m to the membranes where fusion occurs and by engineering sequences with increased binding affinity for gB we have enhanced the antiviral potency of our prototype inhibitors. Our results provide proof of concept for the application of cholesterol tagging to develop inhibitors of HSV-1.

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