Mucin‐Inspired Filamentous Sulfated Copolymers Effectively Inhibit Human Respiratory Syncytial Virus (hRSV) Infectivity

Virucidal compounds capable of binding to and disrupting viruses represent a promising avenue for antiviral applications. In this study, the development of high molecular weight (≈300 kDa) dendronized polyglycerol-based mucin-inspired amphiphilic statistical copolymers (MIACPs) is reported using the RAFT polymerization technique. These copolymers comprise ≈30% repeat units containing aliphatic C11 carbon chains with terminal carboxylate (MIACP-1) and alkyl (MIACP-2) functionalities, while the remaining ≈70% of the repeat units consist of dendronized polyglycerol sulfates. Structural characterization using cryo-electron microscopy (cryo-EM) and small-angle neutron scattering (SANS) reveals that MIACPs form single-chain filamentous structures, similar to natural porcine gastric mucin (PGM). These biocompatible MIACPs exhibit strong, sulfate-dependent inhibition of human respiratory syncytial virus (hRSV), with exceptionally low IC₅₀ values (C = ≈0.25 µg mL^-1). The virucidal activity is assessed using serial dilution experiments, which confirms that MIACPs demonstrate virucidal activity, indicating a very strong binding affinity of the polymers to the hRSV. In contrast, a similar molecular weight homopolymer composed solely of sulfated dendronized repeat units exhibits comparable hRSV inhibition activity but lacks any virucidal effect. Therefore, designing a statistical copolymer with ≈30% virucidal functionality is unique in that it renders the copolymer virucidal without compromising its inhibitory activity.