Plastic Antibodies Mimicking the ACE2 Receptor for Selective Binding of SARS-CoV-2 Spike

Molecular imprinting has proven to be a versatile and simple strategy to obtain selective materials also termed "plastic antibodies" for a wide variety of species, i.e., from ions to macromolecules and viruses. However, to the best of the authors' knowledge, the development of epitope-imprinted polymers for selective binding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not reported to date. An epitope from the SARS-CoV-2 spike protein comprising 17 amino acids is used as a template during the imprinting process. The interactions between the epitope template and organosilane monomers used for the polymer synthesis are predicted via molecular docking simulations. The molecularly imprinted polymer presents a 1.8-fold higher selectivity against the target epitope compared to non-imprinted control polymers. Rebinding studies with pseudoviruses containing SARS-CoV-2 spike protein demonstrate the superior selectivity of the molecularly imprinted matrices, which mimic the interactions of angiotensin-converting enzyme 2 receptors from human cells. The obtained results highlight the potential of SARS-CoV-2 molecularly imprinted polymers for a variety of applications including chem/biosensing and antiviral delivery.