Mucin‐Inspired Single‐Chain Polymer (MIP) Fibers as Potent SARS‐CoV‐2 Inhibitors

• Published in: Angewandte Chemie International Edition Vol. 62; no. 29; pp. e202304010 - n/a
• Main Authors: Bej, Raju, Nie, Chuanxiong, Ludwig, Kai, Ahmadi, Vahid, Trimpert, Jakob, Adler, Julia M., Povolotsky, Tatyana L., Achazi, Katharina, Kagelmacher, Marten, Vidal, Ricardo Martin, Dernedde, Jens, Kaufer, Benedikt B., Haag, Rainer
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 17.07.2023
• Edition: International ed. in English
• Subjects: Addition polymerization; Aqueous solutions; Biocompatibility; Fibers; Molecular weight; Mucin; Mucin-Inspired Polymer; Mucins; Polymers; RAFT Polymerization; SARS-Cov-2 Inhibition; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Single-Chain Fiber; RAFT Polymerization; SARS-Cov-2 Inhibition; Single-Chain Fiber; Biocompatibility; Mucin-Inspired Polymer
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202304010

Mucins are the key component of the defensive mucus barrier. They are extended fibers of very high molecular weight with diverse biological functions depending strongly on their specific structural parameters. Here, we present a mucin‐inspired nanostructure, produced via a synthetic methodology to prepare methacrylate‐based dendronized polysulfates (MIP‐1) on a multi gram‐scale with high molecular weight (MW=450 kDa) and thiol end‐functionalized mucin‐inspired polymer (MIP) via RAFT polymerization. Cryo‐electron tomography (Cryo‐ET) analysis of MIP‐1 confirmed a mucin‐mimetic wormlike single‐chain fiber structure (length=144±59 nm) in aqueous solution. This biocompatible fiber showed promising activity against SARS‐CoV‐2 and its mutant strain, with a remarkable low half maximal (IC50) inhibitory concentration (IC50=10.0 nM). Additionally, we investigate the impact of fiber length on SARS‐CoV‐2 inhibition by testing other functional polymers (MIPs) of varying fiber lengths. Inspired by biological mucus, here, we report multi gram‐scale synthesis of dendronized polysulfates as mucin‐inspired virus‐binding polymer (MIPs). Cryo‐electron tomography (Cryo‐ET) analysis reveals their single chain fiber morphology. These biocompatible synthesized fibers inhibit SARS‐CoV‐2 infection and inhibitory activities depend on the length of the fibers.