Priasha Dutta, Amity University Kolkata
The ongoing COVID-19 pandemic is currently raging across our country, and in its most lethal form by far. While scientists are still carrying out extensive research for a permanent one-size-fits-all cure, there are other forms of treatment and prevention strategies. They include vaccine development, designing of macromolecular neutralizing antibodies, and small-molecule antiviral drugs. Polymeric antibodies have also been designed for playing a role in antiviral drug delivery carriers and for inhibiting the virus effectively. The importance of polymers against Coronavirus disease can be understood below. Polymers can inhibit the COVID spread by-
- providing a semipermeable barrier (e.g., face shield or mask),
- intruding with binding to the glycoprotein surface of host cells,
- enhancing small molecular antiviral drug therapies,
- increasing the response of the immune system as a vaccine adjuvant,
- acting as a carrier for other therapeutic molecules to improve the stability or water solubility of antiviral therapeutics.
The above images show semi-permeable barriers provided by masks and face shields to prevent the entry of coronavirus via the nose, mouth and eyes of a person
Based on the rapid progression, increasing importance, and versatility of biopolymers and polymeric nanoparticles, they can pave the way toward the treatment of this new type of coronavirus. Following are the polymer-based structures and formulations that can inhibit the viral expression in their ways:
- Synthetic polymeric structures capable of direct coronavirus binding:
The fusion of viral and cell membranes occurs by binding between the SARS-CoV-2-related spike (S) protein and angiotensin-converting enzyme 2 (ACE2). Polymers have the ability to directly interfere with the interacting mechanisms of a virus with the host cell. The high molecular weight and polyvalent binding of specifically designed polymers can shield the viral surface or competitively inhibit virus-host cell interactions.
POLYANIONS- The surface of a virus is rich in amino acid residues. SARS-CoV-2 mutation from SARS-CoV causes the removal of some negatively charged amino acids in the former, leading to a stronger electrostatic interaction between SARS-CoV-2 and ACE2 on epithelial cell membranes. Inhibiting this strong electrostatic interaction will inhibit the virus from entering the host cell. Polyanions and polycations can interrupt the binding.
Polyanions like poly(propylacrylic acid), poly(vinyl phosphonic acid) (PVPA), and poly(2-acrylamidoethyl)phosphate have displayed an inhibitory effect on the SARS virus. PVPA has the strongest repressive effect on SARS.
POLYCATIONS- Polycations act as antiviral agents through electrostatic interaction with negatively charged cell membranes or lipid-encapsulated virus envelopes, hence preventing viruses from adsorbing to the cell surface or directly inactivating virus particles. Poly(amidoamine)s (PAMAMs), poly(ethylene imine) (PEI), and their derivatives have inhibitory effects. The negative electrostatic potential of ACE2 receptors is a possible target of polycations to prevent virus binding. PEI with glycosyl modification has unique potential in anti-coronavirus binding.
DENDRITIC POLYMERS- Dendritic are highly branched polymers containing greater solubilities, larger surface areas, and changeable shapes. These structural features can enhance antiviral activity. Polyglycerol sulfate (PGS) is an analog to heparan sulfate, a co-receptor for SARS-CoV-2 mediating entry to host cells. Nanogels based on dendritic PGS is non-toxic with broad-spectrum antiviral activity, inhibiting viruses from binding to the cell surface.
2. Monoclonal-type” plastic antibodies:
Monoclonal antibodies can target the sites on viral surface proteins and block the infection process. However, traditional monoclonal antibodies cannot be used extensively. They are very expensive to produce, have restricted stability, and weakened interactions with the immune system. An alternative to the former is plastic antibodies formed with polymeric biomaterials. Molecular Imprinting is a powerful technology for developing “monoclonal-type” plastic antibodies based on Molecularly Imprinted Polymers (MIPs).
These polymeric materials have specific recognition properties for a target molecule, known as a template. The synthesis of MIPs comprises the polymerization of functional and cross-linking monomers around the template. It is then extracted, resulting in a porous polymeric network containing the binding cavities fitting the size, shape, and other morphological properties of the target compound. MIPs are physically and chemically stable in a wide range of conditions, easily available due to their low cost, and faster and easier to prepare.
“Monoclonal-type” polymeric antibodies that are based on MIPs can selectively bind to a segment of the SARS-CoV-2 spike protein and interfere or block its function, thus, inhibit the infection process. The coronavirus spike protein is a surface dimer that regulates host recognition and attachment. Thus, it is the primary target for the development of antibodies and other therapeutic agents. Polymeric imprinted nanoparticles can be used as drug-free therapeutics in SARS-CoV-2 infection treatment. Plastic antibodies targeting vulnerable sites on viral surface proteins could disable receptor interactions and protect an uninfected host that contains the virus. Nanoparticles when loaded with antiviral drugs can act as a powerful multimodal system; combining their ability to block the virus spike protein with the targeted delivery of the loaded drug. MIPs can be further engineered into a MIP-based sensor for diagnostic purposes or an immunoprotected vaccine.
3. Polymer-based macromolecular prodrugs:
Polymer-based excipients can improve the performance of molecular antivirus drugs by modifying release kinetics and exhibiting complementary antiviral activity, hence improving the therapeutic index of the small-molecule drugs manyfold. For example, ribavirin, a guanosine nucleoside with an ability to intervene in virus mRNA synthesis, has been coupled with certain polyanions to give ribavirin-based macromolecular prodrugs. This prodrug design could maintain the efficacy of ribavirin while decreasing its toxicity. Ribavirin can accumulate in red blood cells (RBCs) and cause hemolytic anemia. Therefore, it is only clinically available to hospitalized patients with severe respiratory infections. Ribavirin polyanionic macromolecular prodrug (PAMP) has been used widely as an antiviral drug against HIV, Ebola virus, influenza, measles, mumps, and dengue. PAMP’s antiviral effect is linked to its ability to block virion binding to the host cell receptor because of both the polyanion component and the inhibitory effect of the nucleoside analog. PAMP has also proven to exhibit the same effects in combating coronavirus in a clinical trial stage.
4.Polymeric delivery systems for vaccine carriers, adjuvants, and antiviral drugs:
Polymers can serve as adjuvants for improving the safety and efficacy of vaccines. A suitable excipient can increase the build-up of vaccine at a disease site and raise an immune response. Polymeric structures can also improve the safety and effectiveness of a vaccine, along with protecting the integrity of encapsulated antigen to prevent its degradation. Polymeric encapsulation can facilitate mucosal administration instead of injection, resulting in higher patient compliance. Polymeric vectors can also be designed with good biocompatibility, a large specific surface area, low immunogenic risk, biodegradability, and a reduction in the required therapeutic dose. Numerous natural polymers have been used for the preparation of nanoparticle vaccine-delivery machinery.
For antiviral drug delivery, poly(ethylene glycol) (PEG) and PEI derivatives have been widely used. These polymeric delivery machineries lessen the side-effects of encapsulated drugs (tablets and capsules), increase their solubility in water, and also improve their efficacy. Natural polysaccharides like chitosan and cyclodextrins are known for the delivery of antiviral drugs like ribavirin, camostat mesylate, lopinavir, nitazoxanide, and ritonavir; all of which produce inhibitory effects on coronavirus. Comparing to synthetic ones, naturally occurring polymers are less toxic with greater biocompatibility. Polysaccharides can activate T lymphocytes, B lymphocytes, macrophages, and other immune cells to generate an immune response.
To sum up, the immense importance of polymers against Coronavirus disease has been justified by various research-based evidence. Polymers against Coronavirus such as polymeric antibodies work as antiviral drug delivery carriers and inhibit the virus effectively. Polymeric structures are also helpful for delivering therapeutic small interfering RNA (siRNA). siRNA can be physically encapsulated in nanoparticles made of PEG, poly(lactic acid- co-glycolic acetic acid) (PLGA), or some dendritic macromolecules. siRNA can effectively and specifically block the gene expression of S protein in SARS-CoV-infected cells. So, an RNA interference strategy might have a strong possibility for SARS-CoV inhibition. poly(amide)-based dendrimer nanocarriers have been proven to act as an aerosol-based siRNA delivery system that could effectively transfect lung epithelial cells in coronavirus treatment. Since ciliated cells of the human lung are the main site of SARS-CoV-2 infection, these polymer-based siRNA delivery systems might have the potential to treat ARS-CoV-2–induced pneumonia.
Also read: Manufacturing Synthetic Polymers from Modified Virus-Resistant Bacteria
References:
- Jiang, X., Li, Z., Young, D. J., Liu, M., Wu, C., Wu, Y. L., & Loh, X. J. (2021). Toward the prevention of coronavirus infection: what role can polymers play?. Materials today. Advances, 10, 100140. https://doi.org/10.1016/j.mtadv.2021.100140
- Parisi, O.I, Dattilo, M., Patitucci, F., Malivindi, R., Pezzi, V., Perrotta, I., Ruffo, M., Amone, F., Puoci, F. (2020). “Monoclonal-type” plastic antibodies for SARS-CoV-2 based on Molecularly Imprinted Polymers” (2020). DOI- https://doi.org/10.1101/2020.05.28.120709
- Ucciferri, C., Vecchiet, J., & Falasca, K. (2020). Role of monoclonal antibody drugs in the treatment of COVID-19. World journal of clinical cases, 8(19), 4280–4285. https://doi.org/10.12998/wjcc.v8.i19.4280
- The Corrosion Prediction from the Corrosion Product Performance
- Nitrogen Resilience in Waterlogged Soybean plants
- Cell Senescence in Type II Diabetes: Therapeutic Potential
- Transgene-Free Canker-Resistant Citrus sinensis with Cas12/RNP
- AI Literacy in Early Childhood Education: Challenges and Opportunities
One thought on “Importance of polymers against Coronavirus disease”