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. The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic highlights the need for fast and efficient response against new viruses. The search for suitable antibodies is an important issue for diagnosis, treatment, and prevention of viral infections. Herein, a plastic antibody based on molecular imprinting using an epitope from SARS‐CoV‐2 spike protein as a template that mimics the action of angiotensin‐converting enzyme 2 receptor is presented.

Plastic Antibodies Mimicking the ACE2 Receptor for Selective Binding of SARS-CoV-2 Spike (Adv. Mater. Interfaces 5/2022)

Plastic Antibodies for Selective Binding of SARS-CoV-2 Spike In article number 2101925, Alex D. Batista, Beatriz Fresco-Cala, and co-workers design and synthesize the very first silane-based silica core/shell molecularly imprinted polymers using an epitope peptide from SARS-CoV-2 spike protein as a template, which can act as a synthetic angiotensin-converting enzyme 2 receptor (ACE2) and bind to SARS-CoV-2. The interactions between the epitope template and the organosilane monomers are predicted via molecular docking simulations.

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.

Development and Characterization of Magnetic SARS-CoV-2 Peptide-Imprinted Polymers.

The development of new methods for the rapid, sensitive, and selective detection of SARS-CoV-2 is a key factor in overcoming the global pandemic that we have been facing for over a year. In this work, we focused on the preparation of magnetic molecularly imprinted polymers (MMIPs) based on the self-polymerization of dopamine at the surface of magnetic nanoparticles (MNPs). Instead of using the whole SARS-CoV-2 virion as a template, a peptide of the viral spike protein, which is present at the viral surface, was innovatively used for the imprinting step. Thus, problems associated with the infectious nature of the virus along with its potential instability when used as a template and under the polymerization conditions were avoided. Dopamine was selected as a functional monomer following a rational computational screening approach that revealed not only a high binding energy of the dopamine-peptide complex but also multi-point interactions across the entire peptide template surface as opposed to other monomers with similar binding affinity. Moreover, variables affecting the imprinting efficiency including polymerization time and amount of peptide and dopamine were experimentally evaluated. Finally, the selectivity of the prepared MMIPs vs. other peptide sequences (i.e., from Zika virus) was evaluated, demonstrating that the developed MMIPs were only specific for the target SARS-CoV-2 peptide.