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 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.This article is protected by copyright. All rights reserved