Polymer modification of SARS-CoV-2 spike protein impacts its ability to bind key receptor

• Published in: European polymer journal Vol. 184; p. 111767
• Main Authors: Sharfin Rahman, Monica, De Alwis Watuthanthrige, Nethmi, Chandrarathne, Bhagya M., Page, Richard C., Konkolewicz, Dominik
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 07-02-2023; Published by Elsevier Ltd
• Subjects: Grafting to; Protein-polymer conjugation; Protein–protein interactions; RAFT; Spike protein; Grafting to; Protein–protein interactions; RAFT; Spike protein; Protein-polymer conjugation
• ISSN: 0014-3057; 1873-1945
• DOI: 10.1016/j.eurpolymj.2022.111767

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•Receptor binding domain of SARS-CoV-2 spike protein was modified with polymers.•Polymer modification led to substantial inhibition of the SARS-CoV-2 spike protein to ACE2.•This work highlights the sensitivity of receptor binding domain to modifications.•This work can aid the design of new therapeutics for COVID-19.
The global spread of SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) has caused the loss of many human lives and severe economic losses. SARS-CoV-2 mediates its infection in humans via the spike glycoprotein. The receptor binding domain of the SARS-CoV-2 spike protein binds to its cognate receptor, angiotensin converting enzyme-2 (ACE2) to initiate viral entry. In this study, we examine how polymer modification of the spike protein receptor binding domain impacts binding to ACE2. The horseradish peroxidase conjugated receptor binding domain was modified with a range of polymers including hydrophilic N,N-dimethylacrylamide, hydrophobic N-isopropylacrylamide, cationic 3-(N,N-dimethylamino)propylacrylamide, and anionic 2-acrylamido-2-methylpropane sulfonic acid polymers. The effect of polymer chain length was observed using N,N-dimethylacrylamide polymers with degrees of polymerization of 5, 10 and 25. Polymer conjugation of the receptor binding domain significantly reduced the interaction with ACE2 protein, as determined by an enzyme-linked immunosorbent assay. Stability analysis showed that these conjugates remained highly stable even after seven days incubation at physiological temperature. Hence, this study provides a detailed view of the effect specific type of modification using a library of polymers with different functionalities in interrupting RBD-ACE2 interaction.