LitCovid-sentences  

PMC:7435837 / 1503-45261 JSONTXT 12 Projects

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Id Subject Object Predicate Lexical cue
T15 0-2 Sentence denotes 1.
T16 3-15 Sentence denotes Introduction
T17 16-181 Sentence denotes In this paper, the role of a layer-by-layer nanocoating approach to provide a mechanism of prevention of the spreading of the corona- and other viruses is described.
T18 182-340 Sentence denotes The emphasis is placed on passive prevention techniques that may contribute to curbing the spread of the pathogen, rather than active pharmaceutical measures.
T19 341-476 Sentence denotes It must be emphasized that the continued efforts toward vaccination and pharmacotherapeutic measures are essential and should continue.
T20 477-606 Sentence denotes It is suggested that our non-pharmaceutical prophylaxis measures will aid the pharmaceutical measures in a complementary fashion.
T21 607-779 Sentence denotes The perspective provided here is that several measures can be taken to prevent the spreading of the pathogen and attempt to combat the virus before it even enters the body.
T22 780-1036 Sentence denotes Despite our description of external measures against coronaviruses, it still relies significantly on the knowledge gained by renowned researchers who have established and studied vaccination and pharmacotherapeutic interventions against viruses in general.
T23 1038-1040 Sentence denotes 2.
T24 1041-1089 Sentence denotes The Cell Entry Mechanism of Encapsulated Viruses
T25 1090-1201 Sentence denotes Encapsulated viruses such as the SARS-CoV and SARS-CoV-2 viruses comprise of some general surface constituents.
T26 1202-1409 Sentence denotes The surface envelope or capsule is presented as a lipid bilayer membrane that contains various envelope proteins (E), membrane proteins (M), and an outer layer that presents so-called spike (S) proteins [1].
T27 1410-1504 Sentence denotes M and S proteins are generally rich in sugar molecules that form a so-called glycan structure.
T28 1505-1655 Sentence denotes N- or O-glycosylate moieties are commonly found in the viral S proteins and they can recognize some cell receptors to which the virion can bind [2,3].
T29 1656-1717 Sentence denotes These spike proteins facilitate virion entry into host cells.
T30 1718-1821 Sentence denotes Encapsulated viruses such as the coronaviruses present approximately 200 of these spiky structures [4].
T31 1822-1974 Sentence denotes Spike proteins are comprised of glycoproteins, proteins that also contain polysaccharide or oligosaccharide moieties otherwise known as glycans [5,6,7].
T32 1975-2171 Sentence denotes The glycoproteins have a variety of functions that maintain the virion structure and properties such as water solubility, creation of diffusion barriers, and antiadhesive actions among others [6].
T33 2172-2405 Sentence denotes In addition to the intrinsic functions that glycoproteins afford to the maintenance of the virion structure, they also act as a structure that recognizes glycan-binding proteins presented on the membranes of potential host cells [1].
T34 2406-2512 Sentence denotes The viral glycans may be recognized by bacterial, fungal, and parasite-associated glycan-binding proteins.
T35 2513-2587 Sentence denotes However, viruses are also recognized by host cells via the same mechanism.
T36 2588-2744 Sentence denotes It is this form of intercellular recognition interactions that prove vital to effect the virus entry into host cells in which the virus could replicate [7].
T37 2745-2865 Sentence denotes A detailed description of the spike glycoproteins of SARS-CoV-2 reported that two binding subunits can be distinguished.
T38 2866-2975 Sentence denotes These subunits become active when the two units are cleaved by host cell proteases on the host cell membrane.
T39 2976-3121 Sentence denotes Subunit, S1 is responsible for binding to the host cell membrane and subunit, S2 is responsible for fusion of the virion and host cell membranes.
T40 3122-3216 Sentence denotes The S1 unit is the factor that makes various coronaviruses specific toward a certain host [8].
T41 3217-3468 Sentence denotes Pulmonary angiotensin-converting-enzyme 2 (ACE-2) in humans exhibit the appropriate receptor, a specific sequence of amino acid residues [9], towards S1 and partly explains the effective spread of the coronaviruses via droplets in the atmosphere [10].
T42 3469-3700 Sentence denotes As part of the human host immune responses, the glycans of the coronavirus spike protein subunits are recognized by dendritic cells [11] in the blood which binds to the glycan and subsequently expresses CD4+ and CD8+ glycopeptides.
T43 3701-3804 Sentence denotes These glycopeptides label the spike protein and this labeled protein is then presented to T-cells [12].
T44 3805-3907 Sentence denotes T-cells subsequently recognize the labels, phagocytose these antigen-marked viruses, and degrade them.
T45 3908-4083 Sentence denotes It has been found that the glycan-binding proteins, also known as lectins [5], can impart broad-spectrum binding properties against HIV-1, SARS-CoV, and human cytomegalovirus.
T46 4084-4222 Sentence denotes The lectin which is capable of showing broad interaction via oligomannosyl antigens is known as lectin GNA (Galanthus nivalis agglutinin).
T47 4223-4352 Sentence denotes The N-oligomannosyl cores are embedded in N-glycans which are commonly expressed on the surface of numerous viral pathogens [13].
T48 4353-4519 Sentence denotes Once the lectin binds to the glycan, the virus structure may undergo conformational changes that result in the fusion of the virus and host to facilitate virus entry.
T49 4520-4602 Sentence denotes S-proteins are specifically responsible for host cell entry by coronaviruses [14].
T50 4603-4680 Sentence denotes Figure 1 depicts a simplified entry mechanism of the viruses into host cells.
T51 4682-4684 Sentence denotes 3.
T52 4685-4745 Sentence denotes Potential Targets for Drug Development against Coronaviruses
T53 4746-4877 Sentence denotes It has been shown at the time of writing that ACE-2 receptors in the lungs are specific targets for SARS-CoV-2 spike proteins [15].
T54 4878-5105 Sentence denotes It has been found that lung parenchyma must be in the differentiated state of the cell cycle and must express the ACE-2 receptor on the apical side, i.e., the site of the first contact with air, of the parenchyma [16,17,18,19].
T55 5106-5225 Sentence denotes It is no surprise therefore that the SARS, MERS, and SARS-CoV-2 viruses cause significant lung injury [20,21,22,23,24].
T56 5226-5437 Sentence denotes ACE-2 is also expressed to a significant extent in the gastrointestinal tract (GIT) [25] which accounts for the GIT symptoms that appeared in SARS-CoV patients and currently in SARS-CoV-2 infected patients [26].
T57 5438-5603 Sentence denotes Current pharmaceutical efforts against coronaviruses aim to interfere with the binding of the viral glycans in their spike proteins to potential host cell receptors.
T58 5604-5761 Sentence denotes The drug umifenovir has been shown to prevent the fusion of viral S-proteins with the host cell ACE-2 receptors, therefore excluding cell entry of the virus.
T59 5762-5854 Sentence denotes However, umifenovir was clinically inefficient to improve the Covid-19 disease outcome [27].
T60 5855-5980 Sentence denotes A contributing membrane-bound enzyme that facilitates spike protein entry via ACE-2 receptors is the TMPRSS2 serine protease.
T61 5981-6161 Sentence denotes This protease primes the coronavirus spike protein for entry by cleaving protein domains that increase the interaction with host cell membranes that result in membrane fusion [28].
T62 6162-6303 Sentence denotes It was also suggested that TMPRSS2 cleaves ACE-2 sites that promote the affinity for the viral spike protein, hence enhances cell entry [29].
T63 6304-6458 Sentence denotes Another possible target for treatment is the inhibition of the synthesis of the required saccharides that are incorporated in the host cell glycoproteins.
T64 6459-6602 Sentence denotes Several quinine derivatives showed that these saccharide moieties known as sialic acids could be inhibited by drugs such as hydroxychloroquine.
T65 6603-6754 Sentence denotes The quinines, therefore, decrease the number of glycan targets that could be engaged by coronaviral spike proteins to facilitate cell entry [30,31,32].
T66 6755-6882 Sentence denotes However, quinine derivatives pose significant cardiotoxicity that precludes their application as a treatment for Covid-19 [33].
T67 6883-7018 Sentence denotes Antiretrovirals such as nelfinavir have proven to be efficient inhibitors of post-entry replication of the virions of SARS-CoV [34,35].
T68 7019-7227 Sentence denotes It has been found that protease inhibitors used in SARS and MERS studies prevented the cleavage and activation of spike proteins following the translation of precursor polypeptides from the viral RNA [36,37].
T69 7228-7325 Sentence denotes RNA is a vital step towards the ultimate formation of the structural protein of new viruses [34].
T70 7326-7476 Sentence denotes Ritonavir and lopinavir [38] have shown some good activity against the SARS-CoV protein cleavage that ultimately prevents spike proteins from forming.
T71 7477-7634 Sentence denotes Some investigated drugs have been reviewed as protease inhibitors against coronaviruses and the reader is referred to the publication by Adedeji et al. [39].
T72 7635-7716 Sentence denotes Figure 2 shows the currently identified targets for which drugs are investigated.
T73 7717-7816 Sentence denotes Vaccination efforts are attempting to create a substrate that can be recognized by dendritic cells.
T74 7817-7931 Sentence denotes The dendritic cells will subsequently label the virus spike proteins with coronavirus specific CD4+/CD8+ peptides.
T75 7932-8053 Sentence denotes These specifically loaded particles will then be presented to T-cells that interact with T-lymphocyte dependent antigens.
T76 8054-8246 Sentence denotes This interaction results in the induction of B-lymphocytes that produces antibodies that can recognize the spike proteins of coronaviruses to afford phagocytosis and destructions of the virus.
T77 8247-8444 Sentence denotes It is also expected that memory T-cells will form which could result in long-term immunity when these cells are replicated when a spike protein can be recognized by dendritic or other immune cells.
T78 8445-8583 Sentence denotes The carbohydrate-based vaccine holds promise to present recognizable glycan arrays that are representative of the targeted pathogens [41].
T79 8584-8797 Sentence denotes Very recently, several targets have been identified for the development of SARS-CoV-2 vaccines that have been identified based on the similarity of the virus to a previously encountered coronavirus, SARS-CoV [42].
T80 8798-9050 Sentence denotes It has been proven that many of the human pathogenic coronaviruses share a significant genomic overlap of more than 99.9% and this provides the basis for developing vaccines from a previously encountered coronavirus infection before SARS-CoV-2 [15,43].
T81 9051-9216 Sentence denotes The Middle East respiratory syndrome-related coronavirus, MERS-CoV, and SARS-CoV form part of these β-coronaviruses which wreaked havoc in the last two decades [44].
T82 9217-9374 Sentence denotes Therefore, one of the most promising targets is the characterization of spike protein epitopes that can be recognized by immune cells such as B- and T-cells.
T83 9375-9616 Sentence denotes Some form of replication of this spike protein epitope should, therefore, be developed and this will hopefully provide the antigens which can bind to, for example, B- or T-cell antibodies and alert the immune system to coronaviruses [44,45].
T84 9617-9764 Sentence denotes A recombinant vaccination approach could be demonstrated by expressing the receptor-binding domain [46] of SARS-CoV spike protein in an adenovirus.
T85 9765-9923 Sentence denotes This recombinant adenovirus was administered nasally and T-cells showed a significant immune response towards the expressed spike protein-binding domain [47].
T86 9924-10073 Sentence denotes Recombinant DNA approaches have made significant strides towards the synthesis of peptide sequences that can directly bind to spike protein epitopes.
T87 10074-10142 Sentence denotes Spike proteins of the MERS-CoV were neutralized in this way [48,49].
T88 10143-10262 Sentence denotes The spike protein antigen of the MERS-CoV was also reported and identified targets for spike protein deactivation [50].
T89 10263-10400 Sentence denotes It is emphasized that the discussion of chemotherapeutic and vaccination efforts is superficial and not covered in detail in this report.
T90 10401-10511 Sentence denotes Of importance though is the fact that antigen-antibody interactions are a key interest in developing vaccines.
T91 10512-10662 Sentence denotes This recognition mechanism is creating the prelude for the discussion of the layer-by-layer nanocoating process that will be elaborated in due course.
T92 10664-10666 Sentence denotes 4.
T93 10667-10737 Sentence denotes The Role of Polysaccharides in the Treatment of Coronavirus Infections
T94 10738-10834 Sentence denotes Mammalian cell membranes are decorated by glycoproteins that contain glycans or polysaccharides.
T95 10835-11040 Sentence denotes As described above, polysaccharides and proteins can interact and if the interaction happened to be between matching polysaccharides and proteins [51], a viral infection, for example, will take place [52].
T96 11041-11229 Sentence denotes Antiviral polysaccharides can, therefore, be very efficient against viral, and other pathogenic, infections if appropriate polysaccharide moieties can be exploited for protein recognition.
T97 11230-11365 Sentence denotes Through recognition of the pathogen mucopolysaccharides, or glycosaminoglycans (GAG), have significant potential to explore drug leads.
T98 11366-11485 Sentence denotes GAG is expressed ubiquitously throughout the body on cell surfaces as well as in the extracellular space between cells.
T99 11486-11639 Sentence denotes An interesting property of these polysaccharides is that they are very diverse in their structure and also not monodisperse, precisely defined molecules.
T100 11640-11765 Sentence denotes Various enzymes are capable of modifying these polysaccharides at various bodily sites to perform a particular function [53].
T101 11766-11902 Sentence denotes GAG is distinguished into four categories namely heparin/heparin sulfate, chondroitin/dermatan sulfate, keratan sulfate, and hyaluronan.
T102 11903-12023 Sentence denotes One can deduce that the GAG biopolymers are sulfated, except for hyaluronic acid [54], and therefore negatively charged.
T103 12024-12129 Sentence denotes GAG is a class of naturally occurring polysaccharides that are commonly described as mucopolysaccharides.
T104 12130-12218 Sentence denotes Mucopolysaccharides are commonly found in the mucous and act as viscous lubricants [55].
T105 12219-12577 Sentence denotes Mucopolysaccharides were traditionally considered to be inert, however, of late have been increasingly more recognized for their immunomodulatory action due to the multipotent recognition of various lectins [55,56,57] or specific protein recognition that often forms the basis from polysaccharide drugs are derived for broad-spectrum antiviral activity [58].
T106 12578-12636 Sentence denotes GAG can also be tailored to elicit specific bioactivities.
T107 12637-12802 Sentence denotes Reported specific examples include the modification of heparin-like structures against for example dengue and flaviviruses [59], herpes simplex 1 and 2 viruses [60].
T108 12803-12974 Sentence denotes GAG-derived drugs can act as a decoy target for viral recognition [61] and therefore prevent cell membrane interaction that will allow virus entry into the host cell [62].
T109 12975-13096 Sentence denotes They also facilitate cell adhesion, cell growth, and differentiation, as well as cell signaling and anticoagulation [55].
T110 13097-13254 Sentence denotes Since these molecules are polymers, numerous sites for binding interactions exist and pathogens might even be capable of incorporating host cell glycans [9].
T111 13255-13463 Sentence denotes Coronaviruses have been known to interact with heparin sulfate proteoglycans, one of the most commonly occurring glycoproteins in eukaryotic organisms, and facilitate virion adsorption to cell membranes [63].
T112 13464-13686 Sentence denotes The spike protein of SARS-CoV-2 is shown to interact with heparin which is derived from the GAG, heparan sulfate and this indicated a potential target for heparan and heparin-derived drugs against SARS-CoV-2 [64,65,66,67].
T113 13687-13782 Sentence denotes Heparan sulfate is a promising target since heparin glycans are widely expressed in lung cells.
T114 13783-13912 Sentence denotes Heparan sulfate is an important co-receptor for ACE-2 since ACE-2 receptor expression is too low to directly result in infection.
T115 13913-14087 Sentence denotes SARS-CoV [68,69] and CoV-NL63 [70] coronaviruses initially bind to heparin sulfate which concentrates the virion concentration close to the ACE-2 receptor for cellular entry.
T116 14088-14319 Sentence denotes Studies involving other SARS-CoV-2-unrelated viruses such as the Ebola virus [71], human metapneumovirus [72], and Ross River virus [73] have also illustrated that the heparan sulfate is a common glycan receptor for viral proteins.
T117 14320-14580 Sentence denotes It is strongly suggested that an electrostatic interaction is to blame for the interaction between negatively charged sulfate groups of GAGs and positively charged arginine amino acid residues of the virion binding S1 subunit responsible for virion adsorption.
T118 14581-14814 Sentence denotes CoV-NL63 [74], hepatitis E virus [75], capsid proteins of adeno-associated virus type 2 [76], and swine fever virus [77] are but a few viruses that indicated cationic electrostatic interaction with negatively charged heparan sulfate.
T119 14815-14924 Sentence denotes It was again found that significant attention is garnered by the development of polysaccharide-derived drugs.
T120 14925-15067 Sentence denotes The focus now shifts on these examples, however, one has to recognize the protein-glycan interaction between pathogen and host cell membranes.
T121 15068-15194 Sentence denotes It is also apparent from the literature that sulfated GAGs are the most potent receptors for a huge variety of virus proteins.
T122 15195-15400 Sentence denotes The occurrence of electrostatic interactions between the spike proteins of coronaviruses, among others, and the prominent GAG, heparan sulfate introduces the discussion on layer-by-layer (LbL) nanocoating.
T123 15402-15404 Sentence denotes 5.
T124 15405-15481 Sentence denotes What Can LbL Nanocoating Contribute to the Prevention of Infectious Disease?
T125 15483-15487 Sentence denotes 5.1.
T126 15488-15535 Sentence denotes The Process of Layer-by-Layer (LbL) Nanocoating
T127 15536-15608 Sentence denotes LbL self-assembly of polyelectrolytes took its origin in the 1990s [78].
T128 15609-15738 Sentence denotes Poly(styrene-4-sulfonate), PSS, was one of the first polyanions employed for LbL self-assembly and remains widely utilized today.
T129 15739-15941 Sentence denotes As polycation, an ammonium-containing polymer, poly(N,N-dimethylallylamine), PDDA, was successfully employed to create a multilayer structure comprising of alternating polyanion and -cation layers [79].
T130 15942-16079 Sentence denotes A series of proteins were also successfully employed as polycations namely cytochrome c, lysozyme, histone f3, myoglobin, and hemoglobin.
T131 16080-16191 Sentence denotes By adjustment of the pH of the medium, amylase, glucose oxidase, and catalase were employed as polyanions [80].
T132 16192-16274 Sentence denotes DNA was also employed successfully as a polyelectrolyte for LL self-assembly [81].
T133 16275-16339 Sentence denotes LbL coating has also been employed to modify inorganic surfaces.
T134 16340-16460 Sentence denotes Although many applications for these surface modifications are possible, only some antimicrobial examples are mentioned.
T135 16461-16552 Sentence denotes Stainless steel surfaces were primed with an acrylate-based surfactant via electrografting.
T136 16553-16625 Sentence denotes Subsequently, PSS and PDDA layers were coated in an alternating fashion.
T137 16626-16726 Sentence denotes Lastly, a layer of chitosan was coated as an antibacterial layer against E. coli and S. aureus [82].
T138 16727-16840 Sentence denotes Silicone-based intraocular lenses (IOL) are commonly employed to replace the natural eye lens when it is damaged.
T139 16841-16985 Sentence denotes The IOL can, however, allow adhesion of many kinds of bacteria and lead to post-operative infections with catastrophic effects in some patients.
T140 16986-17158 Sentence denotes LbL nanocoating of the lenses with hyaluronic and chitosan had significant anti-adhesion and bactericidal effects that reduced the risk of postoperative infections [83,84].
T141 17159-17339 Sentence denotes The technique of LbL nanocoating is uncomplicated and requires relatively low concentrations of the polyelectrolytes to produce an efficient coat, often in the low nanometer range.
T142 17340-17461 Sentence denotes A substrate for coating is required, a polycation and separate polyanion solution, and clean water as the washing liquid.
T143 17462-17497 Sentence denotes Figure 3 illustrates the technique.
T144 17498-17614 Sentence denotes Numerous polysaccharides, especially GAGs, are charged polyelectrolytes and the next section will elaborate on this.
T145 17616-17620 Sentence denotes 5.2.
T146 17621-17667 Sentence denotes Employment of Polysaccharides as LbL Materials
T147 17668-17773 Sentence denotes In this paper, the focus will fall only on common GAGs and other common polysaccharides such as chitosan.
T148 17774-18026 Sentence denotes It was also noticed during our literature survey that the GAG, keratan sulfate has not been studied in LbL applications and can most probably be attributed to its production in the cornea, cartilage, and bone tissues which makes it fairly inaccessible.
T149 18027-18219 Sentence denotes To date, the GAGs and other polysaccharides have not been employed widely in LbL nanocoating to specifically produce antiviral surfaces as is the case for antibacterial or antifungal coatings.
T150 18220-18356 Sentence denotes Numerous publications have reported on the antibacterial surface application of polysaccharides via an LbL approach [85,86,87,88,89,90].
T151 18357-18503 Sentence denotes Table 1 lists some commonly utilized polysaccharides that have been employed in LbL nanocoatings and a non-exhaustive list of recent applications.
T152 18504-18657 Sentence denotes The reader should be able to realize that the LbL technique presents numerous possibilities for the application of polysaccharides as antiviral surfaces.
T153 18658-18729 Sentence denotes Firstly, the polysaccharides, especially GAGs are abundantly available.
T154 18730-18896 Sentence denotes Secondly, they can recognize and interact with proteins via a range of intermolecular forces including electrostatic, hydrogen bonding, and hydrophobic bonding [112].
T155 18897-19055 Sentence denotes Thirdly, the polysaccharides are biological molecules and in the case of LbL applications, need minimal or no modification to perform their intended function.
T156 19056-19144 Sentence denotes Fourthly, fairly low quantities of material need to be deposited to coat the substrates.
T157 19145-19231 Sentence denotes Lastly, they are biocompatible, biodegradable, and most renewable sources of material.
T158 19232-19351 Sentence denotes It is very apt to illustrate the chemical structures of the GAGs and some other selected polysaccharides at this point.
T159 19352-19432 Sentence denotes Figure 4 shows the structures based on the official IUPAC recommendations [113].
T160 19433-19634 Sentence denotes From Figure 4, it is observed that several anionic functional groups are available for electrostatic interaction, however, numerous hydroxyl and carbonyl groups are also available for hydrogen bonding.
T161 19635-19766 Sentence denotes The successful application of polysaccharides as antimicrobials now leads us to the possible preventative measures against viruses.
T162 19768-19770 Sentence denotes 6.
T163 19771-19900 Sentence denotes Targets for LbL Coating and Potential Applications against Coronaviruses as Well as General Antiviral Applications and Challenges
T164 19901-20096 Sentence denotes The applications that are discussed in this section are in a sense a crude method of applying highly sophisticated materials and techniques that were developed for in vivo or diagnostic purposes.
T165 20097-20211 Sentence denotes A so-called nanotrap set of applications has been developed that can be used for the detection of pathogens [114].
T166 20212-20315 Sentence denotes These traps rely on the recognitions between antigens and antibodies that were already discussed above.
T167 20316-20541 Sentence denotes An example of carbohydrate trapping was illustrated for chitosan fibers that were functionalized with sialyllactose, facilitating the capture of influenza viruses via the virus hemagglutinin glycoprotein on its surface [115].
T168 20542-20714 Sentence denotes Carbohydrate microarrays have been reviewed comprehensively [116,117] and these were developed to recognize certain pathogens based on glycan-binding properties of lectins.
T169 20715-20778 Sentence denotes Either glycan or lectin is indicative of a particular pathogen.
T170 20779-20975 Sentence denotes Numerous analytical methods, for example, fluorescence spectrometry, mass spectrometry, and surface plasmon resonance spectrometry methods are employed for qualitative and quantitative techniques.
T171 20977-20981 Sentence denotes 6.1.
T172 20982-21001 Sentence denotes Water Sterilization
T173 21002-21085 Sentence denotes All humans need to drink water and have access to water to ensure personal hygiene.
T174 21086-21215 Sentence denotes In the context of the recommendation to wash hands frequently to remove coronavirus and other pathogens, humans need clean water.
T175 21216-21271 Sentence denotes However, water can easily be contaminated with viruses.
T176 21272-21441 Sentence denotes It was proven that representative coronaviruses, mouse hepatitis virus, and transmissible gastrointestinal virus survived for weeks, even in pasteurized, settled sewage.
T177 21442-21548 Sentence denotes This suggested that sewage and contaminated water sources posed a risk for coronavirus transmission [118].
T178 21549-21725 Sentence denotes Currently, numerous research groups have started to establish if SARS-CoV-2 is present in sewage water and traces of the virus have been found in numerous sewage sources [119].
T179 21726-21937 Sentence denotes SARS-CoV-2 was also recently detected in the stool of an asymptomatic child [120] and remains in the gastrointestinal tract of pediatric patients for a prolonged period even after clearance from the lungs [121].
T180 21938-22158 Sentence denotes It is suggested that the fecal-oral route of transmission should not be excluded as a route of virus transmission [122], however, it is still being investigated if SARS-CoV-2 will spread through contaminated water [123].
T181 22159-22250 Sentence denotes An indirect form of LbL coating was effected by the manufacturing of lignin core particles.
T182 22251-22322 Sentence denotes These lignin cores were coated with prepared cationic lignin particles.
T183 22323-22469 Sentence denotes Negatively charged cowpea chlorotic mottle viruses and the cationic lignin particles were highly effective in removing the viruses from the water.
T184 22470-22547 Sentence denotes It is suggested to develop this material into water filtration devices [124].
T185 22548-22654 Sentence denotes A microfiltration membrane was developed to filter water and reduce viral counts of a model bacteriophage.
T186 22655-22838 Sentence denotes The LbL coating of the filters was performed with the synthetic polycation, poly(ethylene imine) which was covalently immobilized onto the poly(ether sulfone) water membrane material.
T187 22839-23012 Sentence denotes Silver and copper nanoparticles were also coated in the LbL layers, and although an effective antiviral performance was seen, leached markedly into the filtered water [125].
T188 23013-23117 Sentence denotes In a proof-of-concept study, silicon wafers were LbL-coated with synthetic polyelectrolytes in bilayers.
T189 23118-23215 Sentence denotes Antibacterial effects were apparent and also antiviral activity against the H1N1 influenza virus.
T190 23216-23418 Sentence denotes Although the coated material proved to be 100% bactericidal against waterborne bacteria, it demonstrated 60% virucidal activity against an H1N1 droplet after coating three layers of the polyelectrolyte.
T191 23419-23517 Sentence denotes However, as the coating was increased to 7.5 bilayers, 100% virucidal activity was observed [126].
T192 23518-23640 Sentence denotes LbL coating of nanofiltration membranes with gallic acid and PEI could effectively adsorb selected antibiotics from water.
T193 23641-23744 Sentence denotes Although not directly related, an antiviral effect can be envisioned by this kind of LbL coating [127].
T194 23745-23911 Sentence denotes The successful disinfection of aqueous poliovirus and rotavirus solution was achieved by coating glass slides with synthetic poly(ethylene imine), PEI, cations [128].
T195 23912-24108 Sentence denotes Numerous other examples of LbL coatings on surfaces were also shown to be antimicrobial against many waterborne organisms, yet antiviral effects were not reviewed or were simply mentioned briefly.
T196 24109-24290 Sentence denotes It is, however, apparent that the same intermolecular forces that lead to interaction between surfaces and viruses occur between surfaces and other microorganisms [129,130,131,132].
T197 24292-24296 Sentence denotes 6.2.
T198 24297-24311 Sentence denotes Air Filtration
T199 24312-24551 Sentence denotes As with water, coronaviruses survive on inanimate surfaces [133] that include metal, glass, wood, paper, silicon, surgical gloves, plastic, and non-stick PTFE surfaces for a period of up to nine days on plastic and two days on steel [134].
T200 24552-24673 Sentence denotes It was also observed that MERS-CoV could survive in the air for much longer durations than influenza virus strains [135].
T201 24674-24751 Sentence denotes However, living tissue such as mucosal membranes harbors these viruses [136].
T202 24752-24863 Sentence denotes As with the need for water, humans need to breathe and are, therefore, naturally exposed to all these surfaces.
T203 24864-24948 Sentence denotes The need for broad-spectrum protection against airborne microbes has been expressed.
T204 24949-25178 Sentence denotes Three protective measures against airborne spread of viruses have been suggested to ensure the antiviral efficiency of filter materials and lastly, that these materials are not limited to only one type of device or surface [137].
T205 25179-25334 Sentence denotes Wearing facial masks is a commonly recommended prophylactic measure against the spread of airborne pathogens [138,139] such as the influenza A virus [140].
T206 25335-25547 Sentence denotes It is even recommended that patients suspected of being infected with SARS-CoV-2 should be fitted with masks during surgery or procedure requiring anesthesia [141] and also during transport to the hospital [142].
T207 25548-25744 Sentence denotes FFP2 and FFP3/N95 masks offer significant protection against airborne particles and even then the FFP3 masks filter at least 99% of airborne particles, leaving a gap for some particle penetration.
T208 25745-25808 Sentence denotes These masks also still pose the risk of improper sealing [143].
T209 25809-26089 Sentence denotes It has been shown that airborne viruses, for example, norovirus, adenovirus, and torque teno virus can be detected in air samples [144] on for instance PTFE filters that were used to detect SARS-CoV [145], and MERS by the employment of a specialized air sampling instrument [146].
T210 26090-26437 Sentence denotes Several viruses, especially respiratory viruses are effectively distributed by airborne droplets [147,148], and very obviously the human coronaviruses such as SARS-CoV [145,149,150], MERS [146,151,152], and SARS-CoV-2 [153,154,155,156] even though some controversy exists regarding respiratory transmission as the only means of distribution [157].
T211 26438-26495 Sentence denotes Some examples of viral air filtration are discussed next.
T212 26496-26551 Sentence denotes HEPA filters were coated with charged carbon nanotubes.
T213 26552-26710 Sentence denotes During the filtration study, the nanotubes were shown to be 92% effective in the filtration of a viral bacteriophage, MS2, as a model of viral particle [158].
T214 26711-26839 Sentence denotes There are virtually no reports on coated antiviral air filters, let alone employing an LbL coating method to create these masks.
T215 26840-27019 Sentence denotes These are rapid inactivation action, broad-spectrum inactivation not only against specific strains, and lastly universal application on various media, not just facial masks [159].
T216 27020-27159 Sentence denotes The coating of the filter fabric of these masks with PEI achieved more than 99.999% antiviral activity against the T4D bacteriophage virus.
T217 27160-27253 Sentence denotes These coatings were achieved by dip coating, however, LbL nanocoating was not reported [159].
T218 27254-27354 Sentence denotes A disposable polyimide layer has been coated onto porous silicon-based masks, including an N95 mask.
T219 27355-27463 Sentence denotes The layer proved to be hydrophobic and prevented the accumulation of droplets on the mask almost completely.
T220 27464-27538 Sentence denotes The film can be peeled off after use and replaced to reuse the mask [160].
T221 27539-27670 Sentence denotes A comprehensive review of cellulose-based air filters has shown that cellulose is an effective material to produce antiviral masks.
T222 27671-27880 Sentence denotes Cellulose ester materials that are anionic are still seen as the most effective antiviral material in filters and again affirms the potential interaction of positively charged spike proteins and negative GAGs.
T223 27881-27990 Sentence denotes However, LbL nanocoating of cellulose has both been described as a method to produce antiviral filters [161].
T224 27991-28156 Sentence denotes In an unrelated application, our research has shown that cellulose can be coated easily employing LbL coating with, for example, chitosan as coating materials [162].
T225 28157-28278 Sentence denotes It is proposed that it would be possible to modify a facial mask that is based on a cellulose fabric with antiviral GAGs.
T226 28279-28514 Sentence denotes There are indications that LbL nanocoating of air filtration devices can make a significant contribution to the prevention of virus distribution and be very relevant to the prevention of the respiratory variants of human coronaviruses.
T227 28516-28520 Sentence denotes 6.3.
T228 28521-28529 Sentence denotes Textiles
T229 28530-28648 Sentence denotes In addition to wearing facial masks, protective clothing is another important measure against the spread of pathogens.
T230 28649-28731 Sentence denotes Cotton is one of the most commonly employed textiles used to manufacture clothing.
T231 28732-28815 Sentence denotes Cotton fabric, which was ready for use by the textile industry, was LbL nanocoated.
T232 28816-28927 Sentence denotes The alternating layers comprised of PSS and poly(allylamine) bilayers followed by bilayers of PSS and chitosan.
T233 28928-29035 Sentence denotes The coated fabric was washed in water to remove the excess polyelectrolyte with or without ultrasonication.
T234 29036-29137 Sentence denotes The fabric that was washed with ultrasonication produced a more uniformly coated fabric than without.
T235 29138-29350 Sentence denotes The coated material was exposed to antimicrobial tests and significant antibacterial activity was shown toward S. aureus and some activity was still maintained after washing the fabric with a non-ionic detergent.
T236 29351-29493 Sentence denotes Up to 80% of bactericidal activity was maintained for fabric samples that were washed with ultrasonication compared to samples washed without.
T237 29494-29560 Sentence denotes The latter samples retained approximately 30% bactericidal effect.
T238 29561-29607 Sentence denotes Antiviral effects were not investigated [163].
T239 29608-29751 Sentence denotes Chitosan-alginate LbL was also reported to impart antibacterial effects on cotton fabric, however, antiviral activity was not determined [164].
T240 29752-29887 Sentence denotes Chitosan also afforded antibacterial properties when alternately layered with sulfonated lignin or boric acid onto cotton fabric [165].
T241 29888-30073 Sentence denotes Lignin, an abundant product of unexplored commercial value, that is produced from wood pulp during paper manufacturing also impart antibacterial properties to coated textiles [165,166].
T242 30074-30181 Sentence denotes Another popular application of the LbL coating of cotton fabrics was to create flame-retardant cloth [167].
T243 30182-30365 Sentence denotes Examples include the coating of the material with flame-retardant laponite nanoclay particles [168], cationic starch, and montmorillonite nanoclay particles in alternate layers [169].
T244 30366-30537 Sentence denotes Nylon-66, a popular synthetic textile, was also rendered flame-retardant by LbL-nanocoating with cationic chitosan and anionic alginate [170] or anionic phytic acid [171].
T245 30538-30687 Sentence denotes Another synthetic textile, polyester, were coated with synthetic PSS and PDDA to impart significant antibacterial properties to the fabric [172,173].
T246 30688-30890 Sentence denotes Dual-purpose, environmentally friendly, antibacterial, and flame-retardant layers of poly(hexamethylene guanidine phosphate) and the seaweed-derived alginate could also be coated on cotton fabric [174].
T247 30891-31162 Sentence denotes Another example of synthetic polyelectrolyte LbL nanocoating that showed significant antibacterial properties comprises of N-halamine-derived copolymer polyelectrolytes, however, the coated cotton fiber had to be immersed in household bleach to elicit antiviral activity.
T248 31163-31279 Sentence denotes Despite this, the amount of chlorine that was absorbed could be controlled depending on the bilayer thickness [175].
T249 31280-31380 Sentence denotes Another approach to producing a coated textile is to coat fibers that are used to weave the textile.
T250 31381-31493 Sentence denotes Some drug delivery approaches were employed to create chitosan-alginate fibers loaded with a protein drug [176].
T251 31494-31669 Sentence denotes Wood pulp fibers were also successfully LbL-coated with chitosan and carboxymethylcellulose [177] and this fiber coating could, for example, lead to paper strengthening [178].
T252 31670-31788 Sentence denotes Antibacterial vascular grafts were produced by LbL nanocoating of chitosan and heparin onto the graft materials [179].
T253 31789-31894 Sentence denotes It is suggested that pre-coated fibers can be produced and subsequently weaved into an antiviral textile.
T254 31895-31972 Sentence denotes Again, a scarcity of literature was found that focused on antiviral activity.
T255 31973-32108 Sentence denotes It provides an “inside-out” method of textile coating instead of coating the finished textile after it was weaved from uncoated fibers.
T256 32109-32205 Sentence denotes Polysaccharides may again prevail as an effective pre-treatment option prior to weaving fabrics.
T257 32206-32543 Sentence denotes Antiviral activities of polysaccharides, especially of unmodified GAGs or uncomplicated naturally derived polysaccharides such as chitosan and pullulan have been reviewed [180], yet at the time of writing, almost no literature could be found where these polysaccharides were LbL-coated onto textiles specifically for an antiviral effect.
T258 32544-32723 Sentence denotes Antibacterial and improvement of the physical properties of coated textiles seem to be the focus of comprehensive reviews with brief mentioning of antiviral effects [173,181,182].
T259 32724-32871 Sentence denotes Despite the lack of explicit LbL nanocoating of textiles, it is illustrated that coating of fabrics could be an effective antiviral countermeasure.
T260 32872-33056 Sentence denotes Surgical gowns were, for example, laminated with a 3-fold layer of poly(propylene) as the outer layer, PTFE as the middle layer, and a non-woven polyester layer as the innermost layer.
T261 33057-33150 Sentence denotes PTFE proved essential in curbing viral adhesion and penetration through the fabric [183,184].
T262 33151-33282 Sentence denotes A survey of the patent literature also revealed almost no applications of LbL-nanocoating in antiviral settings regarding textiles.
T263 33284-33288 Sentence denotes 6.4.
T264 33289-33304 Sentence denotes Medical Devices
T265 33305-33484 Sentence denotes Seriously ill patients with respiratory distress, and also other patients with other conditions such as cardiovascular disease often require intimate contact with medical devices.
T266 33485-33634 Sentence denotes Examples of devices include prosthetic heart valves, orthopedic implants, intravascular catheters, artificial hearts, cardiac pacemakers, etc. [185].
T267 33635-33760 Sentence denotes Wettability of the surfaces has been shown to play a crucial role in the adhesion of viruses to whichever surface is present.
T268 33761-33933 Sentence denotes Glass slides were successfully coated with silanes of various hydrophobicity and showed that more hydrophobic surfaces were most efficient in capturing influenza A viruses.
T269 33934-34038 Sentence denotes This points again to a form of nanotrapping and inactivation of the virus by surface interactions [186].
T270 34039-34139 Sentence denotes Glass slides were also LbL coated with polyanionic and polycationic chitosan to eliminate S. aureus.
T271 34140-34242 Sentence denotes It was implied that this LbL process will benefit medical devices with antibacterial properties [187].
T272 34243-34405 Sentence denotes Vascular prostheses were coated successfully with alternating layers of human serum albumin and the GAG, heparin, and other carbohydrates such as dextran sulfate.
T273 34406-34573 Sentence denotes These multilayered contacts prevented the clotting factor, fibrinogen from causing thrombosis which is a serious complication of contact with the medical device [188].
T274 34574-35009 Sentence denotes Although not always disclosing full information, self-eliminating coatings on medical devices that comprise mainly of polypeptides were successfully applied to medical devices that could deliver biological substances after implantation into the human body [189], applied to urethral catheters and stents to prevent mucosal tissue of the urethra to block openings of the catheter or stent that will lead to prevention of fluid drainage.
T275 35010-35116 Sentence denotes These coatings also released antimicrobials although antivirals were not mentioned specifically [190,191].
T276 35117-35278 Sentence denotes In a comprehensive review, the future of LbL nanocoating in the medical profession was pointed out, however, antiviral LbL applications were not mentioned [192].
T277 35279-35463 Sentence denotes It was interesting to find that LbL-nanocoating of medical devices also revealed very few literature entries and even fewer regarding coating with polysaccharides or antiviral coating.
T278 35464-35611 Sentence denotes It was reported that catheter silicon tubes that contained chlorohexidine-containing PEG-micelles were coated with poly(acrylic acid) as polyanion.
T279 35612-35706 Sentence denotes Again the purpose of this study was to afford antibacterial action to the silicon tubes [193].
T280 35707-35813 Sentence denotes Dental implants are another medical device that benefited from antibacterial LbL coating with PSS and PAH.
T281 35814-35943 Sentence denotes Metronidazole was coated in the final bilayer and this provided the antibacterial effect to prevent periodontal infections [194].
T282 35944-36096 Sentence denotes It is again apparent, at the time of writing, that antiviral coatings of medical devices have not been the main focus of research or innovation efforts.
T283 36097-36222 Sentence denotes Figure 5 depicts a summary of our suggested methods of contributing in an almost crude, passive way to curb viral infections.
T284 36224-36228 Sentence denotes 6.5.
T285 36229-36282 Sentence denotes Challenges to LbL Nanocoating as an Antiviral Measure
T286 36283-36445 Sentence denotes It is seen from the literature that LbL nanocoating has been successful against many microorganisms, however, it has not seen significant testing against viruses.
T287 36446-36577 Sentence denotes It is uncertain how long a surface will remain efficient in trapping viruses, and regular replacement of the materials is probable.
T288 36578-36753 Sentence denotes Recently [160] it was shown that self-cleaning reusable face masks could be manufactured by coating the textile with hydrophobic silicon dioxide over etched pores of the mask.
T289 36754-36954 Sentence denotes On the other hand, it was shown that superhydrophilic chitosan/carboxymethylcellulose LbL coating of silicone ophthalmic devices encouraged the flow of tears and prevented bacterial biofilm formation.
T290 36955-37066 Sentence denotes The devices also contained antibacterial agents that were released and contributed to the overall effect [195].
T291 37067-37174 Sentence denotes Perhaps polysaccharides can be employed in the same way, however, they might require chemical modification.
T292 37175-37263 Sentence denotes It is also not established if hydro- or hydrophilic coatings will be the most effective.
T293 37264-37414 Sentence denotes It has been illustrated that orthopedic implants could be coated with drug-containing niosomes that prevented bacterial adhesion to the implant [196].
T294 37415-37488 Sentence denotes Other antibacterial coatings almost always contained antibacterial drugs.
T295 37489-37600 Sentence denotes Antiviral drugs are not so abundant and other agents might have to be included in the LbL polysaccharide films.
T296 37601-37632 Sentence denotes These are yet to be identified.
T297 37633-37731 Sentence denotes There are no studies that have reported the saturation load that these coatings might accommodate.
T298 37732-37869 Sentence denotes The disposal of materials that have come in contact with viruses is of concern and protocols for handling this waste should be developed.
T299 37870-37995 Sentence denotes Not only do they contribute to waste production [197], but also possibly to accumulation of a virus at the place of disposal.
T300 37996-38139 Sentence denotes Antibacterial textiles have been utilized to manufacture sportswear, underwear, bedding, mattresses, wound dressings, and hospital gowns [198].
T301 38140-38283 Sentence denotes These items need laundering in order to reuse and pollute water sources, potentially leading to the accumulation of viruses in the water [199].
T302 38284-38497 Sentence denotes Perhaps a disposable product is a better alternative than a reusable product such as illustrated for disposable towels and baths that prevent the accumulation of skin bacteria in patients under nursing care [200].
T303 38498-38605 Sentence denotes Clearly many challenges need to be addressed to ensure the effectiveness of these coatings against viruses.
T304 38606-38778 Sentence denotes The way has, however, been paved by, for example, successful antibacterial and antifungal applications in many settings where humans are exposed to many different surfaces.
T305 38780-38782 Sentence denotes 7.
T306 38783-38810 Sentence denotes Conclusions and Perspective
T307 38811-38860 Sentence denotes Humanity is faced with an unprecedented pandemic.
T308 38861-38982 Sentence denotes It is the best-documented pandemic that the world has seen and this makes it different from previous, historic pandemics.
T309 38983-39102 Sentence denotes However, the SARS-CoV-2 pandemic has elicited a concerted, world effort to attempt and curb the effect of the pandemic.
T310 39103-39259 Sentence denotes If a cynical view is taken, humanity has to realize that this will not be the last pandemic and that potentially worse pandemics will be seen in the future.
T311 39260-39414 Sentence denotes The cusp of antibiotic resistance against many infectious diseases is currently being reached, yet there are even fewer defenses against viral infections.
T312 39415-39630 Sentence denotes However, nature has provided an abundance of tools, which with human ingenuity and unselfish behavior, can contribute greatly to the prevention of pandemics or at least help to control the spread of these pandemics.
T313 39631-39781 Sentence denotes Seen only from an antiviral perspective, many efforts that were launched against other microorganisms can also be effectively applied against viruses.
T314 39782-39881 Sentence denotes Significant research efforts are focused on the treatment of coronaviruses and these will continue.
T315 39882-39987 Sentence denotes Of special interest is the employment of antiviral polysaccharide to create virucidal drugs and vaccines.
T316 39988-40058 Sentence denotes These efforts are aimed primarily at in vivo situations and treatment.
T317 40059-40174 Sentence denotes It is suggested that many of the in vivo knowledge can be applied to ex vivo, the passive effort against pathogens.
T318 40175-40283 Sentence denotes It is known that host cells and viruses interact through glycoprotein and polysaccharide-based interactions.
T319 40284-40499 Sentence denotes Therefore, the pharmacological effort is attempting to disrupt these interactions or the cellular effects that are seen after the virus and host membrane has indeed merged and the viral mechanism is put into motion.
T320 40500-40607 Sentence denotes The human body is a harsh environment and drug delivery and drug development meet these challenges head-on.
T321 40608-40771 Sentence denotes These include, for example, resistance to absorption of therapeutic agents into the body or degradation of therapeutic agents once they are absorbed into the body.
T322 40772-40908 Sentence denotes A clever strategy that is being followed against virus-host cell interaction is to exploit the polysaccharide-lectin recognition system.
T323 40909-41040 Sentence denotes In vivo efforts have shown that administered polysaccharide-based drugs can serve effectively as decoy binding targets for viruses.
T324 41041-41133 Sentence denotes Thus, the interaction with membrane-seated viral recognition mechanisms can be circumvented.
T325 41134-41316 Sentence denotes Another approach is to induce immunity by presenting polysaccharides or oligosaccharides that represent viral glycoproteins of a specific, or numerous, pathogen(s) to B- and T-cells.
T326 41317-41462 Sentence denotes These cells will recognize the xenobiotic polysaccharide and activate the immune system cascade and recognize further viruses and eliminate them.
T327 41463-41615 Sentence denotes If successful, memory cells will be formed and become active when the antigen-antibody, polysaccharide-lectin, interaction occurs in a future infection.
T328 41616-41657 Sentence denotes Our suggestion is almost unsophisticated.
T329 41658-41773 Sentence denotes It is inferred that several surfaces and substrates can be exploited as nanotraps for viruses, outside of the body.
T330 41774-41900 Sentence denotes It might not be farfetched to suggest that the naturally occurring GAGs will be sufficient to gain positive antiviral results.
T331 41901-42023 Sentence denotes GAGs are naturally occurring and abundantly available and are suitable to LbL nanocoating in their crude, unrefined state.
T332 42024-42099 Sentence denotes It might seem obvious that a layer-by-layer nanocoating strategy will work.
T333 42100-42219 Sentence denotes However, literature and patent literature surveys have not revealed a significant effort toward antiviral nanocoatings.
T334 42220-42333 Sentence denotes From the abundant bactericidal reports, it can be deduced that the LbL technique will produce antiviral surfaces.
T335 42334-42514 Sentence denotes However, we foresee success because surface recognition mechanisms between organisms, hosts, and guests, rely on similar principles and that is protein-polysaccharide interactions.
T336 42515-42640 Sentence denotes It is known that numerous polysaccharides have shown antiviral properties and hold significant promise as therapeutic agents.
T337 42641-42773 Sentence denotes It is suggested to LbL-nanocoat the polysaccharides onto several environmental structures with which humans come into contact daily.
T338 42774-43067 Sentence denotes We are also optimistic enough to state that researchers in an industry can be successful in this effort since the technique of LbL nanocoating is straightforward, robust, and based on many types of intermolecular forces that can almost guarantee adhesion of materials to a surface of any kind.
T339 43068-43224 Sentence denotes Numerous examples of LbL nanocoating have been found and described that coat commonly encountered surfaces and produce antibacterial and antifungal actions.
T340 43225-43332 Sentence denotes Investigation of the antiviral effects of polysaccharide LbL coatings should be investigated and developed.
T341 43333-43500 Sentence denotes This is an aspect of LbL nanocoating that has not been investigated to a large extent and is a very lucrative option for antiviral research and industrial cooperation.
T342 43501-43569 Sentence denotes The human, airborne coronavirus are ideal targets for this endeavor.
T343 43570-43758 Sentence denotes Polysaccharides, in vivo or ex vivo, should be explored for their antiviral applications, especially against coronavirus infections that may be recurring or more frequent in our existence.