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

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-OSO 3 ) PDS  with an amide-backbone similar to the native mucin glycoproteins. p(G1AAm-OSO 3 ) 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-OSO 3 ) PDS . Both of the sulfated MIPs show strong HSV-1 inhibition in plaque reduction assays with IC 50 values in lower nanomolar range (< 3 nM) 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 was assessed in pre- and post-infection inhibition assays and clearly visualized their high potential for application using fluorescent microscopy imaging of infected cells. This article is protected by copyright. All rights reserved.