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

Abstract

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-OSO₃)_PDS with an amide-backbone similar to the native mucin glycoproteins is synthesized. p(G1AAm-OSO₃)_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-OSO₃)_PDS is tested. Both of the sulfated MIPs show strong HSV-1 inhibition in plaque reduction assays with IC₅₀ values in lower nanomolar range (<3 × 10⁻⁹ m) 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 is assessed in pre- and post-infection inhibition assays and clearly visualize their high potential for application using fluorescent microscopy imaging of infected cells.