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Antiviral polymers are materials made of repeating molecular subunits that have broad-spectrum effects against several viruses. They have attracted research interest over the years and shown potential for the treatment of difficult viral infections. In this article, we discuss the characteristics, types, uses, exciting novel applications, some challenges, and the future of antiviral polymers.
A polysaccharide polymer consisting of maltotriose units, used in production of oral hygiene products, pullulan-based nanomaterials with antimicrobial activities. Image Credit: Kateryna Kon/Shutterstock.com
Antiviral polymers are materials made of repeating units of large, high molecular weight molecules that can stop the replication of viruses, preventing them from infecting the host.
In the viral replication life cycle, the virus binds and attaches to the cell surface through specific receptor molecules, fuses and enters the cell, releases its genomic material into the cell, replicates its parts, and assembles into a virus, which then escapes from the cell. This process is very fast and can lead to disease in a short time.
Antiviral polymers can interfere with one or more of these stages, preventing the multiplication of viruses and infection. Due to these characteristics, they are given considerable attention as antiviral compounds.
Antiviral polymers can be natural or synthetic. Some natural antiviral polymers include polysaccharides like fucoidan, carrageenan, phosphorothioate oligonucleotides, and chitosan while synthetic ones include sialylated polymers and dendrimers.
Natural polymers are derived directly from microbes, plants, or animals and can be either polysaccharide, proteins, or nucleic acid polymers. Naturally, these are preferred because they are less toxic, more biocompatible, and biodegradable. Polysaccharides are more likely to block the entry of viruses into the cell, while nucleic acid polymers are more likely to interfere with viral replication.
Natural polymers have been tested on many viruses. The antiviral efficacy against SARS-CoV-2 of different carrageenan types has recently been established. In another approach to inhibit HIV-1 viral infection, a delivery method based on a zinc-stabilized nanocomplex of chitosan and chondroitin sulfate was developed to deliver tenofovir. These improvements tend to be more effective against the virus.
Synthetic polymers, unlike natural polymers, may be tailored to enhance antiviral activity against a particular virus type by modifying their molecular weight, charge density, chemical composition, functional group type and degree of functionalization, stability distribution, and degradation.
For example, the FDA-approved VivaGel® dendrimer (SPL7013) is used in the treatment and prevention of HIV and genital herpes. The VivaGel® is made up of 32 sodium (1-naphthyleneyl-3,6-disulphonic acid)-oxyacetamide functional groups and is an anionic G4-poly(L-lysine) dendrimer that has a benzylhydramine-amide-lysine core.
The inherent effectiveness of antiviral polymers is affected by their properties such as molecular weight, charge density, chemical composition, and functional groups that characterize the different types.
Antiviral polymers can be used directly to interfere with stages in the viral replication cycle or help to reduce drug dosage and increase the effectiveness of other drugs. Indirectly, they can be used to engage the immune system to mount a response against viruses by mimicking the viral structure.
Polymers can be designed to block certain viruses by changing their content, molecular weight, functional groups, or chain architecture. Examples of functional groups include carboxylic acid groups, amines, sulfates, and phenols.
In one way of using antiviral polymers, the antiviral drug is protected, stabilized, and delivered to the infection site using the polymer as a matrix. For example, in a study published in the Current Eye Research Journal, the authors coupled Acyclovir, a herpes simplex drug, to tyrosine and glutamate to produce water-soluble amino acid prodrugs for ocular administration of Acyclovir to treat herpes infections. The drug’s effectiveness was enhanced.
The functionalized polymer is utilized as an antiviral drug in another method, attaching to the surface of virus particles to prevent infections. In an Ebola virus model, mannose-functionalized dendrimers have demonstrated potential as potent inhibitors according to a study published in the Bioconjugate Chemistry journal.
For indirect effects, the Infection and Immunity Journal published a study that used mice and showed that chitosan activates the immune system indirectly by promoting the activation of macrophages and natural killer cells against viruses.
As with every antiviral substance, virus inhibition is difficult to achieve mainly because as we mentioned earlier, the virus uses the host's resources and machinery to synthesize its parts. Viruses also mutate quite rapidly. Hence, developing selective antiviral agents without secondary effects on the host cell is challenging.
Furthermore, the mechanism of action of many antiviral polymers is still poorly understood. Therefore, it is difficult to predict the outcomes of treatment or make suitable modifications to enhance their effectiveness.
Beyond the use of antiviral polymers as ingestible chemicals, scientists are currently studying safer and more advantageous ways to employ them in avoiding initial contact with viruses.
Recently, the potential of electrospun polymer composites to deliver antiviral healthcare treatments has attracted considerable interest. Proposals include self-sterilization, reusability, and possible antiviral medication encapsulation as fresh approaches for creating efficient antiviral personal protective equipment (PPE) that can be used in the ongoing COVID-19 pandemic.
In another approach, recent developments in polymer science that employ plasma to etch, graft, coat, and activate polymer surfaces to activate and improve their capabilities are utilized to create smart polymers with virus-capture, virus-detection, virus-repelling, and/or virus-inactivation functions for biomedical applications by taking advantage of the special plasma-specific effects.
Most antiviral polymer research is largely in the early stages. Nevertheless, according to current research findings, both natural and man-made polymers can be used as broad-spectrum antiviral medicines to combat a variety of viral diseases.
Virology is quite advanced and the knowledge base for viruses is vast. While this is quite beneficial, the field of antiviral polymers remains relatively underdeveloped. The antiviral potential of polymers to combat emerging viral infections in the absence of vaccinations requires more preclinical investigation in animal models and human trials. They have the potential to lead to discoveries that will aid in the fight against viral infections.
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Akbari, A., Bigham, A., Rahimkhoei, V., Sharifi, S., Jabbari, E. (2022) Antiviral Polymers: A Review. Polymers 14, 1634. https://doi.org/10.3390/polym14091634
Anand, B.S., Katragadda, S., Nashed, Y.E., Mitra, A.K. (2004) Amino acid prodrugs of acyclovir as possible antiviral agents against ocular HSV-1 infections: interactions with the neutral and cationic amino acid transporter on the corneal epithelium. Current Eye Research 29, 153–166. https://doi.org/10.1080/02713680490504614
Bianculli, R.H., Mase, J.D., Schulz, M.D. (2020) Antiviral Polymers: Past Approaches and Future Possibilities. Macromolecules 53, 9158–9186. https://doi.org/10.1021/acs.macromol.0c01273
Li, J., Wang, W., Jiang, R., Guo, C. (2021) Antiviral Electrospun Polymer Composites: Recent Advances and Opportunities for Tackling COVID-19. Frontiers in Materials 8.
Luczkowiak, J., Sattin, S., Sutkeviciute, I., Reina, J.J., Sánchez-Navarro, M., Thépaut, M., Martínez-Prats, L., Daghetti, A., Fieschi, F., Delgado, R. (2011) Pseudosaccharide functionalized dendrimers as potent inhibitors of DC-SIGN dependent Ebola pseudotyped viral infection. Bioconjugate chemistry 22, 1354–1365. https://pubs.acs.org/doi/10.1021/bc2000403
Ma, C., Nikiforov, A., De Geyter, N., Dai, X., Morent, R., Ostrikov, K. (Ken) (2021) Future antiviral polymers by plasma processing. Progress in Polymer Science 118, 101410. https://doi.org/10.1016/j.progpolymsci.2021.10141
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Blaise Manga Enuh has primary interests in biotechnology and bio-safety, science communication, and bioinformatics. Being a part of a multidisciplinary team, he has been able to collaborate with people of different cultures, identify important project needs, and work with the team to provide solutions towards the accomplishment of desired targets. Over the years he has been able to develop skills that are transferrable to different positions which have helped his accomplish his work.
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