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

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

Mucus lines the epithelial cells at the biological interface and is the first line of defense against multiple viral infection. 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, we investigated synthetic mucin-inspired polymers (MIPs) as potential inhibitors of herpes simplex virus 1 (HSV-1). By using a telechelic RAFT polymerization technique, we synthesized a new dendronized polysulfate p(G1AAm-OSO3)PDS with an amide-backbone similar to the native mucin glycoproteins. p(G1AAm-OSO3)PDS shows mucin-like elongated fiber structure, as revealed in cryo-electron microscopy (cryo-EM) imaging, and we tested its HSV-1 inhibition activity together with its previously reported methacrylate analogue p(G1MA-OSO3)PDS. Both of the sulfated MIPs show strong HSV-1 inhibition in plaque reduction assays with IC50 values in lower nanomolar range (< 3 nM) and demonstrate a high cell compatibility (CC50 > 1.0 mg mL-1) with lower anticoagulant activity than heparin. In addition, the prophylactic and therapeutic activity of both MIPs was assessed in pre- and post-infection inhibition assays and clearly visualized their high potential for application using fluorescent microscopy imaging of infected cells.

Title
657. Mucin-Inspired Polymeric Fibers for Herpes Simplex Virus Type 1 Inhibition
Author
J. Arenhoevel, A.-C. Schmitt, Y. Kerkhoff, V. Ahmadi, E. Quaas, K. Ludwig, K. Achazi, C. Nie, R. Bej, R. Haag
Date
2024
Identifier
DOI: 10.1002/mabi.202400120
Source(s)
Citation
Macrom. Biosci., 2024, in press
Type
Text