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

Abstract

AbstractMucus 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.