“Monoclonal-Type” Plastic Antibodies for COVID-19 Treatment: What Is the Idea?

In late December 2019, an outbreak due to a novel coronavirus, initially called 2019-nCoV, was reported in Wuhan, China [...].

detection of low concentrations of the target compound in urine. Protein sensors based on electroactive MIPs were also fabricated by Zhao et al. employing bovine serum albumin and trypsin as model templates and a linear electro-polymerizable molecularly imprinted polymer as a macromonomer [10].
Some recent studies report the development of MIPs-based sensors for the selective detection of viruses such as Japanese Encephalitis Virus (JEV) and Hepatitis A Virus (HAV) through the Resonance Light Scattering (RLS) technique. In the first work, [11] a magnetic surface molecularly imprinted-resonance light scattering sensor was prepared using Fe 3 O 4 microspheres coated by silicon as imprinting substrates and aminopropyl-triethoxysilane (APTES) as functional monomers for fixing JEV through a polymerization process of tetraethyl-orthosilicate (TEOS). In the second one [12], molecular imprinting resonance light scattering nanoprobes able to selectively bind HAV were fabricated using pH-responsive metal-organic frameworks.
Most of the research studies on MIPs for biomacromolecules, such as proteins and viruses, are focused on the preparation of sensors and probes for the detection of these targets, while only a few works are devoted to the therapeutic use of these polymeric materials.
One example is given by Xu et al. [13], who presented molecularly imprinted polymer nanoparticles able to bind the highly conserved and specific peptide motif SWSNKS (3S), an epitope of the envelope glycoprotein 41 (gp41) of human immunodeficiency virus type 1 (HIV-1). The imprinted nanoparticles were produced by solid-phase synthesis and could find a potential application as artificial antibodies for immunoprotection against HIV.
At this time, Parisi et al. at the Department of Pharmacy, Health and Nutritional Sciences of the University of Calabria, are developing "monoclonal-type" plastic antibodies based on MIPs able to selectively bind a portion of SARS-CoV-2 spike protein to block its function and, thus, the infection process ( Figure 1) [14].
photonic crystals and molecularly imprinted polymers [9]. The resulting sensor exhibited optical properties that change upon detection of low concentrations of the target compound in urine. Protein sensors based on electroactive MIPs were also fabricated by Zhao et al. employing bovine serum albumin and trypsin as model templates and a linear electro-polymerizable molecularly imprinted polymer as a macromonomer [10].
Some recent studies report the development of MIPs-based sensors for the selective detection of viruses such as Japanese Encephalitis Virus (JEV) and Hepatitis A Virus (HAV) through the Resonance Light Scattering (RLS) technique. In the first work, [11] a magnetic surface molecularly imprinted-resonance light scattering sensor was prepared using Fe3O4 microspheres coated by silicon as imprinting substrates and aminopropyl-triethoxysilane (APTES) as functional monomers for fixing JEV through a polymerization process of tetraethyl-orthosilicate (TEOS). In the second one [12], molecular imprinting resonance light scattering nanoprobes able to selectively bind HAV were fabricated using pH-responsive metal-organic frameworks.
Most of the research studies on MIPs for biomacromolecules, such as proteins and viruses, are focused on the preparation of sensors and probes for the detection of these targets, while only a few works are devoted to the therapeutic use of these polymeric materials.
One example is given by Xu et al. [13], who presented molecularly imprinted polymer nanoparticles able to bind the highly conserved and specific peptide motif SWSNKS (3S), an epitope of the envelope glycoprotein 41 (gp41) of human immunodeficiency virus type 1 (HIV-1). The imprinted nanoparticles were produced by solid-phase synthesis and could find a potential application as artificial antibodies for immunoprotection against HIV.
At this time, Parisi et al. at the Department of Pharmacy, Health and Nutritional Sciences of the University of Calabria, are developing "monoclonal-type" plastic antibodies based on MIPs able to selectively bind a portion of SARS-CoV-2 spike protein to block its function and, thus, the infection process (Figure 1.) [14]. The coronavirus spike protein is a surface protein that mediates host recognition and attachment. It consists of two functional subunits: the S1 subunit which contains a receptor-binding domain (RBD) responsible for host cell receptor recognizing and binding, and the S2 subunit which The coronavirus spike protein is a surface protein that mediates host recognition and attachment. It consists of two functional subunits: the S1 subunit which contains a receptor-binding domain (RBD) responsible for host cell receptor recognizing and binding, and the S2 subunit which is involved in the fusion of the viral and host membranes [15]. The spike protein, thus, represents the common and primary target for the development of antibodies, vaccines and therapeutic agents. Therefore, polymeric imprinted nanoparticles could be potentially used as drug-free therapeutics in the treatment of the SARS-CoV-2 infection. Plastic antibodies targeting vulnerable sites on viral surface proteins, indeed, could disable receptor interactions and protect an uninfected host that is exposed to the virus. In vivo applications demand MIPs in the form of nanoparticles and there are evidences that nanoMIPs are not toxic in cell culture or when tested with mice [16].
Moreover, when loaded with antiviral agents, these nanoparticles could act as a powerful multimodal system combining their ability to block the virus spike protein with the targeted delivery of the loaded drug. In addition, the same nanoparticles can be further engineered to become an immunoprotective vaccine or an MIP-based sensor for diagnostic purpose.
Based on these considerations, Molecular Imprinting represents a very promising technology for the preparation of polymeric materials with high selective recognition abilities for a target molecule. On the other hand, the imprinting of biomacromolecules, including peptides, proteins, whole viruses or parts of them, presents several challenges due to the size, solubility, fragile structure and stability of these templates. Moreover, virus and viral components availability is also a key issue. Last but not least, sensitivity and selectivity of these polymeric matrices require further improvement to be comparable to those of natural antibodies.
The research work of Parisi et al. aims to overcome these limits to obtain MIP nanoparticles able to selectively recognize and bind the spike protein of the novel coronavirus and counteract the infection process.