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Mucin-Inspired Polymeric Fibers for Herpes Simplex Virus Type 1 Inhibition

"Arenhoevel, J.; Schmitt, A. C.; Kerkhoff, Y.; Ahmadi, V.; Quaas, E.; Ludwig, K.; Achazi, K.; Nie, C.; Bej, R.; Haag, R." – 2024

Mucus lines the epithelial cells at the biological interface and is the first line of defense against multiple viral infections. Mucins, the gel-forming components of mucus, are high molecular weight glycoproteins and crucial for preventing infections by binding pathogens. Consequently, mimicking mucins is a promising strategy for new synthetic virus inhibitors. In this work, synthetic mucin-inspired polymers (MIPs) as potential inhibitors of herpes simplex virus 1 (HSV-1) are investigated. By using a telechelic reversible addition-fragmentation chain-transfer (RAFT) polymerization technique, a new dendronized polysulfate p(G1AAm-OSO(3))(PDS) with an amide-backbone similar to the native mucin glycoproteins is synthesized. p(G1AAm-OSO(3))(PDS) shows mucin-like elongated fiber structure, as revealed in cryo-electron microscopy (cryo-EM) imaging, and its HSV-1 inhibition activity together with its previously reported methacrylate analogue p(G1MA-OSO(3))(PDS) is tested. Both of the sulfated MIPs show strong HSV-1 inhibition in plaque reduction assays with IC(50) values in lower nanomolar range (<3 x 10(-9) m) and demonstrate a high cell compatibility (CC(50) > 1.0 mg mL(-1)) with lower anticoagulant activity than heparin. In addition, the prophylactic and therapeutic activity of both MIPs is assessed in pre- and post-infection inhibition assays and clearly visualize their high potential for application using fluorescent microscopy imaging of infected cells.

Title
Mucin-Inspired Polymeric Fibers for Herpes Simplex Virus Type 1 Inhibition
Author
"Arenhoevel, J.; Schmitt, A. C.; Kerkhoff, Y.; Ahmadi, V.; Quaas, E.; Ludwig, K.; Achazi, K.; Nie, C.; Bej, R.; Haag, R."
Publisher
Macromol Biosci
Keywords
"*Antiviral Agents/pharmacology/chemistry; *Herpesvirus 1, Human/drug effects; *Mucins/chemistry/metabolism; Animals; biocompatible HSV-1 inhibitors; Chlorocebus aethiops; dendronized polyglycerol sulfates; Herpes Simplex/drug therapy/virology; Humans; mucin-inspired polymers; Polymers/chemistry/pharmacology; single-chain fibers; telechelic RAFT polymer; Vero Cells"
Date
2024
Identifier
1616-5195 (Electronic) 1616-5187 (Linking)
Type
Text