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Mucin-Inspired Single-Chain Polymer (MIP) Fibers as Potent SARS-CoV-2 Inhibitors
Authors:Dr. Raju Bej  Dr. Chuanxiong Nie  Dr. Kai Ludwig  Dr. Vahid Ahmadi  Dr. Jakob Trimpert  Julia M. Adler  Dr. Tatyana L. Povolotsky  Dr. Katharina Achazi  Marten Kagelmacher  Ricardo Martin Vidal  Dr. Jens Dernedde  Dr. Benedikt B. Kaufer  Prof. Dr. Rainer Haag
Affiliation:1. Institut für Chemie und Biochemie, Freie Universität Berlin, Takustraße 3, 14195 Berlin, Germany;2. Institut für Virologie, Freie Universität Berlin, Robert-von-Ostertag-Straße 7–13, 14163 Berlin, Germany;3. Institut für Laboratoriumsmedizin, Klinische Chemie und Pathobiochemie, Charité—Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
Abstract: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.
Keywords:Biocompatibility  Mucin-Inspired Polymer  RAFT Polymerization  SARS-Cov-2 Inhibition  Single-Chain Fiber
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