key: cord-1041531-utxk2gbs authors: Jiang, Xiaojuan; Li, Zibiao; Young, David James; Liu, Minting; Wu, Caisheng; Wu, Yun- Long; Loh, Xian Jun title: Towards the Prevention of Coronavirus Infection: What Role Can Polymers Play? date: 2021-03-20 journal: Mater Today Adv DOI: 10.1016/j.mtadv.2021.100140 sha: c0c5de6512d7e58be1f6190bc3e1fde214b789f9 doc_id: 1041531 cord_uid: utxk2gbs Severe Acute Respiratory Syndrome associated coronavirus 2 (SARS-CoV-2) has caused a global public health crisis with high rates of infection and mortality. Treatment and prevention approaches include vaccine development, the design of small molecule antiviral drugs and macromolecular neutralizing antibodies. Polymers have been designed for effective virus inhibition and as anti-viral drug delivery carriers.. This review summarizes recent progress and provides a perspective on polymer based approaches for the treatment and prevention of coronavirus infection. These polymer-based partners include polyanion/polycations, dendritic polymers, macromolecular prodrugs and polymeric drug delivery systems that have the potential to significantly improve the efficacy of antiviral therapeutics. Severe acute respiratory syndrome associated coronavirus 2 or SARS-CoV-2 belongs to the β family of coronaviruses and infects humans by the fusion of viral and cell membranes, facilitated by binding between the SARS-CoV-2-related spike (S) protein and angiotensin-converting enzyme 2 (ACE2) [1] [2] [3] . The β coronavirus family is also responsible for the common cold, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome associated coronavirus (MERS-CoV) 4, 5 . Strategies to reduce coronavirus infection includes wearing masks 6-10 , small molecule drugs 11, 12 , vaccines, neutralizing antibodies 13-15 , RNA interference therapy 16, 17 and other mitigation factors 18 . These treatment methods span in vitro prevention to in vivo treatment, including blocking the spread of the virus, inhibiting the translation of viral RNA in host cells, activating the immune system and inhibiting the expression of S protein gene.) Some of these interventions, however, would benefit from a polymer "modulator" to improve efficacy. There has been some work in literature that describes disinfection as well as anti-microbial materials. [19] [20] [21] [22] [23] [24] Recently, polymer materials have demonstrated antiviral capabilities. As shown in figure 1, polymers can prevent or inhibit the spread of a virus by: (i) providing a semi-permeable barriers (e.g. mask or face-shield); (ii) interfering with binding to the glycoprotein surface of host cells; (iii) augmenting small molecular anti-viral drug therapies; (iv) enhancing the response of the immune system as a vaccine adjuvant; or (v) as a vehicle for other therapeutic molecules to improve the water solubility or stability of anti-viral therapeutics. Based on the structural characteristics and uses of the above polymers, this review will summarize recent polymeric anti-viral approaches based on polyanion/polycation, dendritic polymer, macromolecular prodrugs, and polymer-based delivery system, as well as and the middle filter layer (the core part, as a barrier to block viral particles). The core filter layer of the mask is generally made from electret treated polypropylene melt-blown non-woven fabric, which can reach 95% filterability. Melt-blown, non-woven fabrics have a much higher filtration efficiency than fabrics of cotton, polyester, nylon or silk. The polypropylene is triboelectrically charged to enhance filtration efficiency. Polypropylene is more hydrophobic and so repels moisture in the air, providing a protective environment 28 . In another case, the effect of polytetrafluoroethylene/polyurethane (PETF/PU) membranes in chemical protective clothing was evaluated. Excellent isolation performance against poliovirus was demonstrated and a possible protective mechanism against SARS virus was inferred. 29 This ultra-high filtration efficiency has proved to be an effectively block to the intrusion of coronavirus. Polymers can directly interfere with the interactions of a virus with the host cell. The high molecular weight and multivalent binding of specifically designed polymers can sterically shield the viral surface or competitive inhibit virus -host cell interactions 30 . The next section summaries recent advances in this field by category of polymer. The surface of a virus is rich in amino acid residues. For example, the envelope protein gp120 of human immunodeficiency virus (HIV) is rich in positively charged arginine and lysine. Polyanions, therefore can electrostatically bind to the gp120 protein and prevent HIV from interacting with the host cell's surface. Similarly, severe acute respiratory syndrome associated coronavirus (SARS-CoV) or SARS-CoV-2 has a spike (S) glycoprotein, which binds to the angiotensin I converting enzyme 2 (ACE2) protein as an important step in host epithelial cell invasion. SARS-CoV-2 has the D480→S456 mutation relative to SARS-CoV that J o u r n a l P r e -p r o o f 6 removes some negatively charged amino acids in the former leading to an even stronger electrostatic interaction between ACE2 on epithelial cell membranes and SARS-CoV-2(as shown in Figure. While PVBzA and PEI both exhibit a broad-spectrum antiviral effect, which helps reduces drug resistance, their limitation is potential toxicity that has not been assessed, and large-scale clinical still need to be conducted. HS is a co-receptor for SARS-CoV-2 mediating entry to host cells 45 . Non-toxic and broad-spectrum dendritic nanogels could therefore be potential components of a coronavirus therapy (as shown in Figure. 3A,3B) 46 . Polymers can serve as delivery systems and adjuvants for improving the safety Polymers can also be designed with a low immunogenic risk, good biocompatibility, a large specific surface area, biodegradability and a reduction in the therapeutic dose required [61] [62] [63] [64] [65] [66] . Several natural and synthetic polymers have been used for preparing nanoparticle vaccine delivery vehicles ( Table 1) . 13 Cyclodextrin-based, self-assembled polymer nanoparticles improves siRNA delivery 98, 99 . Likewise, higher molecular weight chitosan provided better complexation ability and increase stability of siRNA polyelectrolyte complexes (polyplex) 100 J o u r n a l P r e -p r o o f Severe Acute Respiratory Syndrome associated coronavirus 2 (SARS-CoV-2) has caused a global public health, crisis with high rates of infection and mortality. In conventional treatment programs, there are disadvantages such as time-consuming and high cost. There is also an added worry that the next pandemic may be even more dangerous. Thoughts around a super-infectious Disease X needing ultra-low virus dose to infect and working on the combination of the aerosol transmission as well as the asymptomatic infection. This will be a disastrous recipe that will make a pandemic of a Disease X very difficult to control. As an emerging field of antiviral properties, polymers have inestimable prospects. Polymers will play an important role in the fight against coronavirus infections, from providing better semi-permeable barriers to air-borne particles, to important partners in chemotherapeutic treatments. Polymer vaccine adjuvants provide improved humoral immunity and administration routes. Polymeric nanocarriers of small molecule antiviral drugs assist local or sustained delivery and assist to overcome poor aqueous solubility and drug resistance. Last, but not least, polymeric structures with targeted gene delivery ability have the potential to silence or disturb the activity of coronaviruses. Polyanions/polycations, dendritic polymers, macromolecular prodrugs and polymeric drug delivery systems have a bright future in this respect. The current evidence shows that its advantages are irreplaceable in conventional treatment programs. There will be new polymer discoveries, some enabled by new technologies, or new scientific capabilities and knowledge which did not exist before. It is hoped that the development of polymers will advance rapidly in the future and move towards clinical treatment as soon as possible. We hope that this summary of recent advances in polymer bioscience will stimulate more discoveries to meet an increasing challenge for a growing human population. We can learn about the technological solutions, research into new technologies, and dig into the our archives to find and develop solutions. Some could be new research from which we derive early research data, some of these will be built on research done over the past several decades. J o u r n a l P r e -p r o o f Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2 Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates Neutralizing Antibodies against SARS-CoV-2 and Other Human Coronaviruses Inhibition of SARS-associated coronavirus infection and replication by RNA interference Valorization of disposable COVID-19 mask through the thermo-chemical process Protective Action of Linear Polyethylenimine against Staphylococcus aureus Colonization and Exaggerated Inflammation in Vitro and in Vivo Wound healing properties of magnesium mineralized antimicrobial nanofibre dressings containing chondroitin sulphate-a comparison between blend and core-shell nanofibres Cationic Poly ([R] -3 -hydroxybutyrate) Copolymers as Antimicrobial Agents Sanitizing agents for virus inactivation and disinfection Toward Nanotechnology-Enabled Approaches against the COVID-19 Pandemic Physical distancing, face masks, and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19: a systematic review and meta-analysis. Lancet 2020, 30 Comparing the Binding Interactions in the Receptor Binding Domains of SARS-CoV-2 and SARS-CoV Influence of sulfur amino acids on copper toxicity in chicks Antiviral activity of polyacrylic and polymethacrylic acids. II. Mode of action in vivo Macromolecular Antiviral Agents against Zika, Ebola, SARS, and Other Pathogenic Viruses Novel quaternary phosphonium-type cationic polyacrylamide and elucidation of dual-functional antibacterial/antiviral activity Polyethyleneimine is a potent mucosal adjuvant for viral glycoprotein antigens Decreasing Herpes Simplex Viral Infectivity in Solution by Surface-Immobilized and Suspended N,N-Dodecyl Griffithsin carrageenan fast dissolving inserts prevent SHIV HSV-2 and HPV infections in vivo Cholesterol dependence of Newcastle Disease Virus entry Murine coronavirus requires lipid rafts for virus entry and cell-cell fusion but not for virus release The Important Role of Lipid Raft-Mediated Attachment in the Infection of Cultured Cells by Coronavirus Infectious Bronchitis Virus Beaudette Strain Modified cyclodextrins as broad-spectrum antivirals Macromolecular prodrugs of ribavirin: towards a treatment for co-infection with HIV and HCV Macromolecular prodrugs of ribavirin combat side effects and toxicity with no loss of activity of the drug Polyanionic Macromolecular Prodrugs of Ribavirin: Antiviral Agents with a Broad Spectrum of Activity Macromolecular prodrugs of ribavirin: Polymer backbone defines blood safety, drug release, and efficacy of anti-inflammatory effects Polymer-Based Nanomaterials and Applications for Vaccines and Drugs A new highly transparent injectable PHA-based thermogelling vitreous substitute Recent Progress in Polyhydroxyalkanoates-Based Copolymers for Biomedical Applications Zinc diethyldithiocarbamate as a catalyst for synthesising biomedically-relevant thermogelling polyurethanes Recent advances in supramolecular hydrogels for biomedical applications Supramolecular thermogels from branched PCL-containing polyurethanes Induction of Robust Immune Responses by CpG-ODN-Loaded Hollow Polymeric Nanoparticles for Antiviral and Vaccine Applications in Chickens Viromimetic STING Agonist-Loaded Hollow Polymeric Nanoparticles for Safe and Effective Vaccination against Middle East Respiratory Syndrome Coronavirus Poly (d,l-lactide-co-glycolide) nanoparticle-entrapped vaccine induces a protective immune response against porcine epidemic diarrhea virus infection in piglets Adjuvanted poly(lactic-co-glycolic) acid nanoparticle-entrapped inactivated porcine reproductive and respiratory syndrome virus vaccine elicits cross-protective immune response in pigs Preparation and efficacy of Newcastle disease virus DNA vaccine encapsulated in PLGA nanoparticles PLGA nanoparticle entrapped killed porcine reproductive and respiratory syndrome virus vaccine helps in viral clearance in pigs Nanoparticulate vacuolar ATPase blocker exhibits potent host-targeted antiviral activity against feline coronavirus O-2'-hydroxypropyltrimethyl ammonium chloride chitosan nanoparticles for the delivery of live Newcastle disease vaccine Quaternized chitosan nanoparticles loaded with the combined attenuated live vaccine against Newcastle disease and infectious bronchitis elicit immune response in chicken after intranasal administration Enhancing Mucosal Immune Response of Newcastle Disease Virus DNA Vaccine Using N-2-Hydroxypropyl Trimethylammonium Chloride Chitosan and N,O-Carboxymethyl Chitosan Nanoparticles as Delivery Carrier Chitosan, hydroxypropyltrimethyl ammonium chloride chitosan and sulfated chitosan nanoparticles as adjuvants for inactivated Newcastle disease vaccine Adjuvant effects of chitosan and calcium phosphate particles in an inactivated Newcastle disease vaccine Preparation and efficacy of a live newcastle disease virus vaccine encapsulated in chitosan nanoparticles Preparation and efficacy of Newcastle disease virus DNA vaccine encapsulated in chitosan nanoparticles Chitosan-coated poly(lactic-co-glycolic) acid nanoparticles as an efficient delivery system for Newcastle disease virus DNA vaccine Intranasal immunization with plasmid DNA encoding spike protein of SARS-coronavirus/polyethylenimine nanoparticles elicits antigen-specific humoral and cellular immune responses DNA vaccine encoding spike protein of SARS-coronavirus loaded polyethylenimine elicits antigen-specific immune responses in mice immunized through intranasal route (42.8) Induction of Dendritic Cell Maturation and Activation by a Potential Adjuvant, 2-Hydroxypropyl-beta-Cyclodextrin Optimization of an mRNA vaccine assisted with cyclodextrin-polyethyleneimine conjugates Improved antiviral activity in vitro of ribavirin against measles virus after complexation with cyclodextrins Characterization of cyclodextrin complexes of camostat mesylate by ESI mass spectrometry and NMR spectroscopy Enhanced stability of oral insulin in targeted peptide ligand trimethyl chitosan nanoparticles against trypsin Cyclodextrin solubilization and complexation of antiretroviral drug lopinavir: In silico prediction; Effects of derivatization, molar ratio and preparation method Strategies, design, and chemistry in siRNA delivery systems Lactosylated poly(ethylene glycol)-siRNA conjugate through acid-labile beta-thiopropionate linkage to construct pH-sensitive polyion complex micelles achieving enhanced gene silencing in hepatoma cells Local and systemic delivery of VEGF siRNA using polyelectrolyte complex micelles for effective treatment of cancer Self-assembled siRNA-PLGA conjugate micelles for gene silencing Alkane-modified short polyethyleneimine for siRNA delivery In vivo endothelial siRNA delivery using polymeric nanoparticles with low molecular weight The first targeted delivery of siRNA in humans via a self-assembling, cyclodextrin polymer-based nanoparticle: from concept to clinic Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles RNA interference in vitro and in vivo using a novel chitosan/siRNA nanoparticle system High efficiency gene transfer using chitosan/DNA nanoparticles with specific combinations of molecular weight and degree of deacetylation Redox-sensitive dendrimersomes assembled from amphiphilic Janus dendrimers for siRNA delivery Highly Efficient and Safe Delivery of VEGF siRNA by Bioreducible Fluorinated Peptide Dendrimers for Cancer Therapy Silencing SARS-CoV Spike protein expression in cultured cells by RNA interference Inhibition of SARS-CoV replication by siRNA Using siRNA in prophylactic and therapeutic regimens against SARS coronavirus in Rhesus macaque dendrimer nanocarriers and their aerosol formulations for siRNA delivery to the lung epithelium