LitCovid-sentences  

PMC:7358770 / 1872-39072 JSONTXT 15 Projects

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Id Subject Object Predicate Lexical cue
T17 0-15 Sentence denotes 1 Introduction
T18 16-279 Sentence denotes The present outbreak of a coronavirus-associated acute respiratory disease called coronavirus disease 19 (COVID-19) has spread to >210 countries, which is rare among acute infectious diseases in recent years, and caused a great threat to global public health [1].
T19 280-471 Sentence denotes This disease was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and it is the third documented spillover of an animal coronavirus to humans in only two decades [2,3].
T20 472-612 Sentence denotes Since the first human coronavirus detected in the 1960s, SARS-CoV-2 is the seventh coronavirus that is known to infect humans (Fig. 1 ) [4].
T21 613-739 Sentence denotes There are four types of coronaviruses named as α, β, γ and δ, which only α- and β-type contain human pathogenic strains [1,4].
T22 740-910 Sentence denotes SARS-CoV-2, including severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), are all β-coronal viruses [3].
T23 911-993 Sentence denotes Fig. 1 The virus types and symptoms of 7 important pathogenic human coronaviruses.
T24 994-1205 Sentence denotes Coronaviruses (CoVs) are enveloped single-stranded positive-sense RNA viruses (Fig. 2A), which widely infected vertebrates including humans and animals, to cause respiratory and enteric diseases [[5], [6], [7]].
T25 1206-1389 Sentence denotes Spike glycoprotein (S protein) plays a major role in the pathogenesis of coronavirus, inducing host immune responses, and is considered a primary target for vaccine preparation [1,8].
T26 1390-1555 Sentence denotes Current information indicates that SARS-CoV-2 is more contagious than SARS-CoV including person­to­person spread, which poses a serious threat to human health [3,9].
T27 1556-1666 Sentence denotes Fig. 2 The structure of CoV virion and S protein, (A) Depiction of the CoV virion; (B) Depiction of S protein.
T28 1667-2231 Sentence denotes A single S protein is depicted as a rectangle, and relevant structural features are highlighted as follows: N-terminal receptor binding domain (N-RBD) in dark blue; C-RBD in brown; cleavage sites (CS) 1 and 2, fusion peptide (FP) in red, heptad repeat (HR) regions 1 and 2 in green; transmembrane span (TM) depicted as membrane bilayer; cytoplasmic tail (CT) in light blue.; (C) Structure of the MHV N-RBD in complex with its CEACAM receptor.; (D) Structure of the SARS C-RBD in complex with its ACE2 receptor.; (E) Structure of the post-fusion HR1-HR2 bundle [7].
T29 2232-2303 Sentence denotes At present, there are almost no specific drugs for coronavirus therapy.
T30 2304-2440 Sentence denotes Researchers have been working to inhibit growth of the virus, but the virus may mutate and develop resistance to these therapies [1,10].
T31 2441-2631 Sentence denotes It is urgent for the international medical community to develop targeted, high-efficiency and low-toxic drugs to treat the coronavirus based on the structure and property of the coronavirus.
T32 2632-2835 Sentence denotes Polysaccharides have been used in traditional Chinese herbal medicine for at least 500 years [11], and have advantages of wide sources, low toxicity, good biocompatibility, and immune regulation [12,13].
T33 2836-3014 Sentence denotes Some polysaccharides, such as carrageenan, chitosan, fucoidan, and astragalus polysaccharide (APS), have been reported to show strong antiviral activity [[14], [15], [16], [17]].
T34 3015-3270 Sentence denotes In particular, sulfated polysaccharides can interfere with the entry process of virus by blocking the positive charge of the pathogen surface receptors, to prevent them from binding to heparan sulfate proteoglycan (HSPGs) on the surface of host cell [18].
T35 3271-3361 Sentence denotes Thus, polysaccharides are attractive candidates for developing potential antiviral agents.
T36 3362-3653 Sentence denotes Here, we summarized and analyzed the antiviral properties, mechanisms, and applications of some polysaccharides and their derivatives in the anti-virus field, aiming to provide a new approach to the development of drugs and vaccines for the treatment of coronavirus, especially for COVID-19.
T37 3655-3718 Sentence denotes 2 Application prospects of polysaccharides against coronavirus
T38 3719-3822 Sentence denotes Polysaccharides are macromolecular compounds obtained mainly from plants, algae, and even animals [15].
T39 3823-3996 Sentence denotes The antiviral properties of polysaccharides are not only a simple function of their charge density and chain length, but also their detailed structural characteristics [19].
T40 3997-4184 Sentence denotes Coronaviruses, such as SARS-CoV, MERS-CoV, and novel SARS-CoV-2, cause high mortality and pose a severe threat to humans and animals health, creating a need for effective inhibitors [20].
T41 4185-4442 Sentence denotes Polysaccharides, which are commonly used active ingredients in traditional Chinese medicine, have a great application prospect in the prevention and treatment of coronavirus based on their broad-spectrum antiviral activities and unique antiviral mechanisms.
T42 4443-4690 Sentence denotes The presence of carbohydrate-binding agents can strongly inhibit coronaviruses, including transmissible gastroenteritis virus, infectious bronchitis virus (IBV), feline coronaviruses serotypes I and II, mouse hepatitis virus (MHV), and PRRSV [21].
T43 4692-4736 Sentence denotes 2.1 Source and structure of polysaccharides
T44 4737-4934 Sentence denotes The main sources of polysaccharides are endogenous glycosaminoglycans (GAGs), Marine polysaccharides and terrestrial plant polysaccharides, especially polysaccharides from Chinese herbal medicines.
T45 4935-5202 Sentence denotes GAGs are naturally-derived linear polysaccharides that are expressed in the intracellular compartments, cell surface, and extracellular environments, and they interact with various molecules to regulate many cellular processes associated with health and disease [22].
T46 5203-5405 Sentence denotes GAGs are comprised distinct O-linked disaccharide units, which are typically composed of a combination of iduronic acid, glucuronic acid, glucosamine, galactose or galactosamine monosaccharides [23,24].
T47 5406-5545 Sentence denotes The widely studied GAGs mainly include chondroitin sulfate (CS), heparan sulfate (HS) and heparin (HP) in animal tissues (Fig. 3 ) [22,25].
T48 5546-5682 Sentence denotes GAG chains are in most cases sulfated, except hyaluronan (HA) (Fig. 3), which are biodegradable and non-immunogenic in the body [26,27].
T49 5683-5743 Sentence denotes The chemical structures of typical GAGs are shown in Fig. 3.
T50 5744-5863 Sentence denotes Fig. 3 The structures of several polysaccharides (GAGs, marine polysaccharides, and terrestrial plant polysaccharides).
T51 5864-5917 Sentence denotes Marine organisms are rich sources of polysaccharides.
T52 5918-6134 Sentence denotes Chitosan is a linear, positive-charged, alkaline polysaccharide repeating by glucosamine and N-acetylglucosamine (Fig. 3) [28,29], derived from the shells of shrimps and crustacean or the cell walls of fungi [30,31].
T53 6135-6324 Sentence denotes Marine algae products have been applied in traditional Chinese herbal medicine for a long time [11], and contain a variety of polysaccharides, including carrageenan, fucoidan, and alginate.
T54 6325-6711 Sentence denotes Carrageenans are sulphated linear polysaccharides composed of repeating disaccharide units with alternating 3-linked β-d-galactopyranose (G-units) and 4-linked α-galactopyranose (D-units) or 3,6-anhydro-α- galactopyranose (AnGal-units) [[32], [33], [34]], which are extracted from certain red algae containing 15–40% ester sulfate with an average molecular weight above 100 kDa [35,36].
T55 6712-6883 Sentence denotes The three commercial most important and widely distributed carrageenans are iota (ι-, G4S-DA2S), kappa (κ-, G4S-DA) and lambda (λ-, G2S-D2S, 6S)-carrageenan (Fig. 3) [37].
T56 6884-7169 Sentence denotes Fucoidan is a fucose-enriched and sulfated polysaccharide extracted from brown algae [11,38], which is composed of L-fucose, sulfate groups and small proportions of D-xylose, D-mannose, D-galactose, and D-glucuronic acid in different sources of brown algae (Fig. 3) [[38], [39], [40]].
T57 7170-7338 Sentence denotes Alginate, an acidic and linear polysaccharide extracted from brown algae, is consisted of alternating β-D-mannuronic acid (M) and α- L-guluronic acid (G) residues [41].
T58 7339-7542 Sentence denotes Polyguluronate sulfate (PGS) (Fig. 3) is a low molecular weight sulfated brown algae polysaccharide obtained by chemical sulfation of polyguluronate (PG) with about 1.5 sulfate per sugar residue [42,43].
T59 7543-7791 Sentence denotes Astragalus polysaccharide (APS) is the most important bioactive component isolated from a Chinese traditional herbal medicine of Astragalus membranaceus, which is composed of glucose, mannose, d-glucose, and D-galactose (Fig. 3) [[44], [45], [46]].
T60 7792-7957 Sentence denotes Radix Isatidis (RI) is also a kind of traditional Chinese herbal medicine with significant antiviral effect, and polysaccharide is its main active component [47,48].
T61 7958-8054 Sentence denotes The polysaccharide from RI is mainly composed of mannose, glucose, galactose and arabinose [49].
T62 8055-8154 Sentence denotes Mushrooms are used as food for long time in China, and also are drugs in the Orient centuries [50].
T63 8155-8284 Sentence denotes Lentinus edodes is one of the most widely edible mushrooms, and is popularly consumed as health foods in Asian countries [50,51].
T64 8285-8516 Sentence denotes Among the bioactive components of mushrooms, the Lentinus edodes polysaccharide (lentinan, LNT) is the most extensively investigated with many immune processes, which is generally described as biological response modifiers [52,53].
T65 8517-8668 Sentence denotes It consists of a β-(1 → 3)-glucan backbone with β-(1 → 6)-glucosyl side-branching units terminated by mannosyl or galactosyl residues (Fig. 3) [50,51].
T66 8669-8772 Sentence denotes Recently, LNT has been widely used as an alternative medicine and dietary supplement in the world [50].
T67 8774-8812 Sentence denotes 2.2 Anti-coronavirus activity of GAGs
T68 8813-8975 Sentence denotes Cell surface GAGs serve as co-receptors by increasing the local concentration of pathogens, so that they can more efficiently interact with their entry receptors.
T69 8976-9114 Sentence denotes Most coronavirus receptors of carbohydrate are mainly negatively charged, such as sulfated GAGs or glycans containing sialic acid [54,55].
T70 9115-9299 Sentence denotes S protein concentrated outside the virus contains the receptor binding domains (RBDs) at the N-terminal, such as MHV-CoV N-RBD and SARS C-RBD with their receptor (Fig. 2B–D) [7,56,57].
T71 9300-9461 Sentence denotes The coronavirus NL63 (CoV-NL63), and SARS-CoV use angiotensin-converting enzyme 2 (ACE2) as a primary receptor for infection of target cells (Fig. 2) [56,58,59].
T72 9462-9633 Sentence denotes Phylogenetically, SARS-CoV-2 is almost identical to SARS-CoV, sharing 79.6% genomic sequence identity [60], and use the same cell entry receptor, ACE2, as SARS-CoV [8,60].
T73 9634-9856 Sentence denotes During infection, CoV first binds host cell via interaction between its S1-RBD and the cell membrane receptor, triggering conformational changes in the S2 subunit that result in virus fusion and entry into the target cell.
T74 9857-10016 Sentence denotes Viral RNA gradually forms mature virions through replication, transcription, and synthesis, and then is released from host cell (Fig. 4 ) [8,[60], [61], [62]].
T75 10017-10180 Sentence denotes However, the expression of ACE2 is not sufficient for infection, and HSPGs play important roles in the entry of some pathogens such as SARS-CoV [[63], [64], [65]].
T76 10181-10282 Sentence denotes A soluble HS was used to assess whether the attachment of HCoV-NL63 was mediated by HS proteoglycans.
T77 10283-10522 Sentence denotes Flow cytometric analysis showed that the adhesion of virus to LLC-Mk2 cells was completely inhibited in the presence of soluble HS, indicating the role of this molecule in adhesion to susceptible cells and possible also in cell entry [54].
T78 10523-10709 Sentence denotes Both CoV-NL63 and SARS-CoV initially bind to the HS on the cell surface, and virus entry depends on the HS interaction, indicating that HS can inhibit virus attachment and entry [22,54].
T79 10710-10760 Sentence denotes Fig. 4 Life cycle of highly pathogenic human CoVs.
T80 10761-10871 Sentence denotes These CoVs enter host cells by first binding to their respective cellular receptors via the surface S protein.
T81 10872-10948 Sentence denotes Viral genomic RNA is released and translated into viral polymerase proteins.
T82 10949-11242 Sentence denotes Viral RNA and nucleocapsid (N) structural protein are replicated, transcribed, or synthesized in the cytoplasm, whereas other viral structural proteins, including S, membrane (M), and envelope (E), are transcribed then translated in the endoplasmic reticulum (ER) and transported to the Golgi.
T83 11243-11423 Sentence denotes The viral RNA–N complex and S, M, and E proteins are further assembled in the ER–Golgi intermediate compartment (ERGIC) to form a mature virion, then released from host cells [62].
T84 11424-11596 Sentence denotes Natural products of HS and the allied polysaccharide, heparin, are involved and prevent infection by a range of viruses including S-associated coronavirus strain HSR1 [66].
T85 11597-11708 Sentence denotes HS is known to bind CoV surface proteins and to be used by coronavirus for its attachment to target cells [54].
T86 11709-11877 Sentence denotes Currently, there are no commercially available medicinal products designed to treat and/or prevent infections associated with the novel SARS-CoV-2 coronavirus outbreak.
T87 11878-12044 Sentence denotes The surface plasmon resonance and circular dichroism were used to measure the interaction between the SARS-CoV-2 Spike S1 protein RBD (SARS-CoV-2 S1 RBD) and heparin.
T88 12045-12139 Sentence denotes Additionally, basic amino acids are known to dictate the binding between proteins and heparin.
T89 12140-12408 Sentence denotes Primary sequence analysis of the expressed protein domain and analysis of the modeled SARS-CoV-2 S1 RBD structure show that there are several potential heparin binding sites, and more importantly, theses patches of basic amino acids are exposed on the protein surface.
T90 12409-12578 Sentence denotes This study has implications for the rapid development of a first-line therapeutic by repurposing heparin and for next-generation, tailor-made, GAG-based antivirals [66].
T91 12580-12636 Sentence denotes 2.3 Anti-coronavirus activity of marine polysaccharides
T92 12637-12836 Sentence denotes Marine polysaccharides, such as carrageenan, PGS, chitosan, and their derivatives, show good inhibitory activity against various viruses, which provides a reference for their research on coronavirus.
T93 12837-13074 Sentence denotes Iota-carrageenan containing lozenges show highly active against human rhinovirus (HRV), influenza virus A H1N1, and HCoV OC43 throughout the entire dissolution process, and are a promising therapy against viral infections of throat [67].
T94 13075-13510 Sentence denotes The cationically modified chitosan, N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC), shows significant inhibition against the human coronavirus HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1, and its hydrophobically modified derivative (HM-HTCC) is a potent inhibitor of the coronavirus HCoV-NL63, indicating that HTCC polymers based on chitosan are effective inhibitors of all low-pathogenic human coronaviruses [68].
T95 13511-13693 Sentence denotes Acute viral upper respiratory tract infection, also known as common cold, is mainly caused by respiratory viruses such as rhinovirus, coronavirus, influenza virus [[69], [70], [71]].
T96 13694-13815 Sentence denotes Clinical trials applying iota-carrageenan nasal spray have shown to reduce the duration of a virus-confirmed common cold.
T97 13816-14039 Sentence denotes Carrageenan nasal spray shows significant antiviral efficacy in three virus subgroups, HRV, human coronavirus, and influenza A virus (IAV), and the highest effectiveness was observed in human corona virus-infected patients.
T98 14040-14243 Sentence denotes The reduced duration of disease was 3 days (p < 0.01), and the number of relapses was three times less (p < 0.01) in carrageenan treated corona-virus -infected patients compared to control patients [70].
T99 14244-14375 Sentence denotes After the outbreak of SARS in 2003, many survivors developed residual pulmonary fibrosis with increased severity in older patients.
T100 14376-14540 Sentence denotes Pulmonary fibrosis is caused by a hyperactive host response to lung injury mediated by epidermal growth factor receptor (EGFR) signaling in animal models (Fig. 5 ).
T101 14541-14669 Sentence denotes Inhibition of EGFR signaling can prevent an excessive fibrotic response to SARS-CoV and other respiratory viral infections [72].
T102 14670-14863 Sentence denotes Moreover, sulfated polysaccharides such as fucoidan and sulfated rhamnan, can interfere or inhibit the expression and activation of EGFR pathway, which may help to suppress coronavirus [73,74].
T103 14864-15025 Sentence denotes The understanding of how polysaccharides play a role in EGFR and other pro-fibrotic pathways after viral infection will provide new ideas for COVID-19 treatment.
T104 15026-15096 Sentence denotes Fig. 5 The illustration about potential role of EGFR in lung fibrosis.
T105 15097-15251 Sentence denotes Physical injury or a pathogen ① initiates the wound healing response by damaging healthy tissue, releasing EGFR ligands ② and activating the EGFR pathway.
T106 15252-15335 Sentence denotes This results in an exaggerated wound healing response leading to a fibrotic lung ③.
T107 15336-15456 Sentence denotes The early use of inhibitors like tyrosine kinase ④ could prevent the normal progress of wound healing and fibrosis [72].
T108 15458-15536 Sentence denotes 2.4 Anti-coronavirus activity of traditional Chinese medicine polysaccharides
T109 15537-15663 Sentence denotes Traditional Chinese herbal medicine is widely used in the prevention and treatment of viral infectious diseases in China [75].
T110 15664-15890 Sentence denotes Some Chinese herbs contain potential anti-SARS-CoV-2 active compounds, especially Hedysarum multijugum maxim, coptidis rhizoma, and forsythiae fructus, which have been catalogued for treating viral respiratory infections [76].
T111 15891-15996 Sentence denotes This provides a basis for the application of traditional Chinese medicine polysaccharides in coronavirus.
T112 15997-16135 Sentence denotes The avian coronavirus causes infectious bronchitis (IB), which is one of the most serious diseases affecting the avian industry worldwide.
T113 16136-16261 Sentence denotes APS can significantly reduce the replication of IBV in infected chicken embryo kidney (CEK) cells in a dose-dependent manner.
T114 16262-16466 Sentence denotes The titer of IBV-specific antibodies, lymphocyte proliferation, and the expression levels of interleukin (IL)-1β, IL-2, IL-8, and TNF-a in APS treatment groups were higher than those in the control group.
T115 16467-16620 Sentence denotes These data suggest that APS enhances the immune response to IBV vaccination in chickens, and is a potential therapeutic agent for inhibiting IBV [77,78].
T116 16621-16745 Sentence denotes During the outbreak of SARS coronaviruses in China, RI, as a Chinese medicinal herb, was prepared as an antiviral drug [79].
T117 16746-17022 Sentence denotes Polysaccharides isolated from RI have been shown to stimulate the expression of cytokines, such as IL-2 and interferon (INF)-γ, thereby regulating and enhancing non-specific immunological function, humoral immunity and cellular immunity in mice to play antiviral effects [48].
T118 17023-17461 Sentence denotes Active compounds derived from cultured Lentinula edodes mycelia (AHCC) is an α-glucan-based standardized mushroom extract that has been extensively investigated as an immunostimulant both in animals and in humans affected by influenza virus, herpes virus, avian influenza virus (AIV), human papillomavirus (HPV), hepatitis B virus (HBV), and human immunodeficiency virus (HIV) by promoting a regulated and protective immune response [80].
T119 17462-17676 Sentence denotes Due to its action in promoting a protective response to a wide range of viral infections, which can support its use in the prevention of diseases provoked by a human pathogenic coronavirus, including COVID-19 [80].
T120 17678-17729 Sentence denotes 3 Polysaccharides have unique antiviral mechanisms
T121 17730-17833 Sentence denotes The antiviral mechanism of polysaccharides is usually related to its specific structure and virus type.
T122 17834-17929 Sentence denotes Coronaviruses are enveloped positive-stranded RNA viruses that replicate in the cytoplasm [81].
T123 17930-18166 Sentence denotes To deliver the nucleocapsid into host cell, the coronavirus-cell entry procedure involves the fusion of the envelope with the host cell membrane mediated by viral S proteins (Fig. 2) [7,81], which is the main determinant of virus entry.
T124 18168-18204 Sentence denotes 3.1 Directly interacting with virus
T125 18205-18404 Sentence denotes Polysaccharides, especially sulfated polysaccharides, can interact with the surface of virus by negative charge, thereby inhibiting the infectious ability of the virus, or killing the virus directly.
T126 18405-18599 Sentence denotes Pathogens use GAGs at almost every major entry portal to promote their attachment and invasion of host cells, to move from one cell to another, and to protect themselves from immune attack [22].
T127 18600-18926 Sentence denotes For example, fucosylated chondroitin sulfate was effective in blocking laboratory strain HIV-1IIIB entry and replication (4.26 μg/mL and 0.73 μg/mL, respectively), and inhibiting infection by clinic isolate HIV-1KM018 and HIV-1TC-2 (23.75 μg/mL and 31.86 μg/mL, respectively) as well as suppressing HIV-1 drug-resistant virus.
T128 18927-19085 Sentence denotes Further studies indicated that fucosylated chondroitin sulfate can potently bind the recombinant HIV-1 gp120 protein to inhibit several strains of HIV-1 [82].
T129 19086-19206 Sentence denotes A cationically modified chitosan derivative, HTCC, has been shown to be an effective inhibitor of HCoV-NL63 replication.
T130 19207-19389 Sentence denotes The analysis of the interaction between HTCC polymer and the recombinant ectodomain of the S protein from CoV showed binding, resulting in the formation of protein-polymer complexes.
T131 19390-19483 Sentence denotes One may assume that such binding will result in the efficient inactivation of the virus [83].
T132 19484-19580 Sentence denotes Carrageenan acts primarily by preventing the binding or the entry of virions into cells [84,85].
T133 19581-19721 Sentence denotes Iota-carrageenan, a high molecular weight sulfated polysaccharide, is an approved antiviral drug that interacts with the viral surface [67].
T134 19722-19820 Sentence denotes The binding and inactivation of virus particles by iota-carrageenan are fast and highly effective.
T135 19821-19987 Sentence denotes During the residence time of the iota-carrageenan containing lozenge in the mouth, the viral titer is reduced by 85% and 91% for IAV and HCoV-OC43, respectively [67].
T136 19988-20217 Sentence denotes Furthermore, animal experiments have shown that iota-carrageenan can reduce the spreading of influenza virus in surface epithelia of infected animals, and thereby provided sufficient benefits for animals to promote survival [86].
T137 20219-20264 Sentence denotes 3.2 Inhibiting virus adsorption and invasion
T138 20265-20440 Sentence denotes The first step for virus to invade a cell is to bind to the cell surface by electrostatic interaction or a receptor, such as heparan sulfated proteoglycan on the cell surface.
T139 20441-20630 Sentence denotes Polysaccharides, especially sulfated polysaccharides, have strong polyanionic properties, and can block the positive charge on the cell surface to prevent virus adsorption or invasion [12].
T140 20631-20788 Sentence denotes The invasion process of virus is often associated with the endocytosis of virus, the fusion of virus with cell membrane, and the translocation of virus [12].
T141 20789-21020 Sentence denotes Heparin or heparin-like materials with broad-spectrum antiviral properties [[87], [88], [89]] have been developed to mimic the cell surface carbohydrates responsible for initial viral attachment, such as HS and carrageenan [34,90].
T142 21021-21182 Sentence denotes The sulfated polysaccharide derived from marine microalga showed strong inhibition against IAV infection via the viral adsorption and internalization steps [91].
T143 21183-21330 Sentence denotes The antiviral effect of sulfated polysaccharides from seaweeds was mainly exerted during dengue virus (DENV)-2 adsorption and internalization [92].
T144 21331-21623 Sentence denotes Iota-carrageenan and its N-sulfonated derivatives of poly (allylamine) hydrochloride showed strong antiviral activities against human metapneumovirus (hMPV), a kind of respiratory infections RNA virus, by blocking virus release from the cellular membrane and inhibiting virus adsorption [93].
T145 21624-21741 Sentence denotes Iota-carrageenan also effectively prevents the replication of HRV in primary human nasal epithelial cells in culture.
T146 21742-21866 Sentence denotes The data suggest that iota-carrageenan acts primarily by preventing the binding or the entry of virions into the cells [85].
T147 21867-21978 Sentence denotes Fucoidan can bind to the neuraminidase (NA) of IAV, and inhibit the activity of NA to block the release of IAV.
T148 21979-22157 Sentence denotes Additionally, fucoidan can also interfere with the activation of EGFR, PKCα, NF-κB, and Akt, and inhibit both IAV endocytosis and EGFR internalization in IAV-infected cells [73].
T149 22158-22289 Sentence denotes The antiviral mechanism of the fucoidans may be through blocking herpes simplex virus (HSV)-2 virion adsorption to host cells [94].
T150 22290-22491 Sentence denotes Our team found that 3,6-O-sulfated chitosan (36S) possessed broad anti-HPV activities by directly targeting viral capsid protein and host PI3K/Akt/mTOR pathway to inhibit cell autophagy (Fig. 6 ) [95].
T151 22492-22723 Sentence denotes Interestingly, using HCoV-NL63 as a model system, it can be determined that HTCC polymer blocks the interaction between S protein and cell receptor, consequently blocking its entry into cells and preventing virus infection [68,96].
T152 22724-22889 Sentence denotes The nano/microspheres of N-(2-hydroxypropyl) -3-trimethyl chitosan (HTCC-NS/MS) were used for adsorption of the coronavirus HCoV-NL63 from aqueous virus suspensions.
T153 22890-23022 Sentence denotes This nano/microspheres can be applied for the removal of coronaviruses and purification of water from pathogenic coronaviruses [97].
T154 23023-23091 Sentence denotes Fig. 6 The mechanism of 3,6-O-sulfated chitosan inhibiting HBV [95].
T155 23093-23144 Sentence denotes 3.3 Inhibiting viral transcription and replication
T156 23145-23296 Sentence denotes Polysaccharides, especially sulfated polysaccharides, can directly interfere with viral replication related enzymes and relevant targets in host cells.
T157 23297-23498 Sentence denotes Iota-carrageenan can effectively inhibit porcine reproductive and respiratory syndrome virus (PRRSV) replication at mRNA and protein levels in both Marc-145 cells and porcine alveolar macrophages [98].
T158 23499-23692 Sentence denotes Carrageenan oligosaccharide and its sulphated derivative have good inhibitory effects on IAV replication both in vitro and in vivo, while not seem to be dependent on the interferon system [99].
T159 23693-23861 Sentence denotes Sulfated polysaccharide from Gracilaria lemaneiformis shows anti-influenza virus activities in vitro by inhibiting viral adsorption and replication on host cells [100].
T160 23862-24088 Sentence denotes Polysaccharides isolated from Grifola frondosa showed resistance against enterovirus 71, a positive-stranded RNA virus, by blocking viral replication and inhibiting viral VP1 protein expression and genomic RNA synthesis [101].
T161 24089-24315 Sentence denotes The virus replication was inhibited by a sulfated polysaccharide from Angelica sinensis, which is a commonly used traditional Chinese herbal medicine, at the dose of 10 and 30 mg/kg (26% and 30% inhibition respectively) [102].
T162 24316-24468 Sentence denotes APS has a long-lasting inhibitory effect on HBV replication in vivo, which can be used as a supplementary modality to treat hepatitis B infection [103].
T163 24469-24568 Sentence denotes Furthermore, APS can inhibit the replication of avian IBV in vitro in a dose-dependent manner [78].
T164 24570-24624 Sentence denotes 3.4 Activating host antiviral immunomodulatory system
T165 24625-24871 Sentence denotes After the virus invades the host, it will trigger the host's immune response, such as regulating the host NK and macrophages cells, inducing the production of immune cytokines, and indirectly exert antiviral effects by activating innate immunity.
T166 24872-25189 Sentence denotes Chitosan can enhance antigen-specific immune responses by increasing the induction of regulatory T cells, lung resident T cells, and neutralizing antibodies while reversing Th2-skewed immune responses induced by inactivated respiratory syncytial virus (RSV) vaccine without affecting lung histopathology in mice [13].
T167 25190-25380 Sentence denotes The sulphated-carrageenan from red alga showed a strong effect on tobacco mosaic virus (TMV) infection by affecting virus accumulation/infectivity and enhancing locally plant immunity [104].
T168 25381-25526 Sentence denotes APS can significantly enhance the immunological function of chicken erythrocytes after infected with infectious bursa disease virus (IBDV) [105].
T169 25527-25650 Sentence denotes Additionally, APS can reduce the replication of H9N2 AIV and promote early humoral immune responses in young chickens [17].
T170 25651-25884 Sentence denotes LNT can significantly down-regulate the expression level of TNF-α, IL-2 and IL-11, and up-modulate the expression levels of IFN-1 and IFN-γ after challenging with infectious hematopoietic necrosis virus (IHNV), which is an RNA virus.
T171 25885-26059 Sentence denotes The results indicate that the inhibitory effects of LNT on IHNV infection are possibly attributed to its regulation of the innate immune responses and specific immunity [51].
T172 26060-26224 Sentence denotes In addition, our team found that PGS, a sulfated derivative of alginate, can effectively inhibit the expression and secretion of HBsAg and HBeAg in HepG2.2.15cells.
T173 26225-26426 Sentence denotes The anti-HBV mechanism of PGS may be associated with appropriate activation of NF-κB and Raf/MEK/ERK signaling pathways to enhance the interferon system, and interfere with HBV transcription (Fig. 7 ).
T174 26427-26581 Sentence denotes This study suggested that PGS merits further investigation as a novel anti-HBV agent aimed at modulating the host innate immune system in the future [42].
T175 26582-26671 Sentence denotes These studies bring new ideas to the development of current anti-novel coronavirus drugs.
T176 26672-26736 Sentence denotes Fig. 7 The molecular mechanisms of PGS inhibits HBV replication.
T177 26737-26872 Sentence denotes Cellular NF-κB and Raf/MEK/ERK signaling pathways are associated with the activation of innate immune system such as interferon system.
T178 26873-27046 Sentence denotes PGS can bind and enter into HepG2.2.15 cells to activate the NF-κB and Raf/MEK/ERK pathways to enhance the interferon system, and indirectly suppress HBV transcription [42].
T179 27048-27096 Sentence denotes 4 Polysaccharide adjuvant for antiviral vaccine
T180 27097-27285 Sentence denotes Vaccination is the most successful and effective medical intervention to prevent infectious diseases, which can reduce mortality, prolong life expectancy and improve quality of life [106].
T181 27286-27460 Sentence denotes The development of a vaccine for coronavirus is a critical step in prevention, but it may not be effective for future strains, and we must be ready for the next epidemic [3].
T182 27461-27657 Sentence denotes Polysaccharide adjuvant can enhance the immune effect of a vaccine, thus promoting body-specific immunity and non-specific immunity, cellular immunity, humoral immunity and mucosal immunity [107].
T183 27658-27899 Sentence denotes Chitosan is effective in stimulating humoral and cell-mediated immune responses with a proven safety record in animals and humans, which has been used as adjuvant for improving vaccine efficacy, especially in RNA virus vaccines [13,108,109].
T184 27900-28108 Sentence denotes Chitosan can only modestly protect animals against RSV infection when given post-infection, while it can significantly reduce RSV infection in mice when combined with inactivated RSV vaccine before infection.
T185 28109-28216 Sentence denotes This study suggested that chitosan can be applied as a potential treatment/adjuvant for RSV infection [13].
T186 28217-28377 Sentence denotes Chitosan-adjuvanted vaccines can enhance antibody titers against A- and B-type human influenza viruses 4 to 6 times compared with the vaccines without chitosan.
T187 28378-28595 Sentence denotes Inactivated AIV A/H5N2 admixed with chitosan, when administered to mice challenged afterwards with the same virus, showed higher immunogenicity and protective efficacy compared with the antigen without chitosan [110].
T188 28596-28698 Sentence denotes Chitosan adjuvanted vaccine stored at 4 °C can preserve its adjuvant properties for at least 8 months.
T189 28699-28807 Sentence denotes Chitosan can stimulate proliferative and cytotoxic activity of splenic mononuclear leukocytes in mice [111].
T190 28808-28975 Sentence denotes Thus, chitosan is a promising adjuvant candidate for inactivated influenza vaccines, which provides a reference for the development of anti-novel coronavirus vaccines.
T191 28976-29215 Sentence denotes Although SARS-CoV vaccines can protect against lethal infection, the addition of delta inulin-based polysaccharide adjuvant on day 3 post-challenge can significantly increase serum neutralizing-antibody titers and reduce lung virus titers.
T192 29216-29376 Sentence denotes It also shows that immunity achieved with delta inulin adjuvants is long-lived, thereby overcoming the natural tendency for rapidly waning coronavirus immunity.
T193 29377-29505 Sentence denotes This suggests that delta inulin polysaccharide adjuvants have the potential to develop more effective coronavirus vaccines [20].
T194 29506-29629 Sentence denotes In addition, some Chinese herbal medicinal polysaccharides have been used as safe and effective adjuvants [77,107,112,113].
T195 29630-29776 Sentence denotes APS as an adjuvant combined with influenza vaccine can improve the immune response and systemic humoral response to H5N1 virus infection [46,114].
T196 29777-29950 Sentence denotes APS can potentially be used as an immunomodulator for a foot-and-mouth disease virus (FMDV), which is an RNA virus vaccine, and provide better protection against FMDV [115].
T197 29951-30158 Sentence denotes APS is also a potent adjuvant for hepatitis B DNA vaccine, and can enhance the immune responses of HBV DNA vaccine via promoting dendritic cells maturation and inhibit the regulatory T cells frequency [116].
T198 30159-30317 Sentence denotes Polysaccharide extract from RI exerts potent anti-IAV activity against human seasonal influenza viruses (H1N1 and H3N2) and AIV (H6N2 and H9N2) in vitro [49].
T199 30318-30487 Sentence denotes The polysaccharides also significantly reduced the expression of pro-inflammatory cytokines (IL-6) and strongly inhibited the protein expression of TLR-3 induced by PR8.
T200 30488-30639 Sentence denotes The polysaccharide extract from RI, therefore, has the potential to be used as an adjunct to antiviral therapy for the treatment of IAV infection [49].
T201 30640-30782 Sentence denotes Additionally, peptide-based vaccines have become as a potentially important strategy for the development of therapeutic vaccination [117,118].
T202 30783-30929 Sentence denotes They do not require in vitro culture, making them biologically safe, and their selectivity can accurately activate the immune responses [119,120].
T203 30930-31082 Sentence denotes For example, a hydrocarbon-stapled short α-helical peptide can effectively inhibit MERS-CoV infection and its S protein-mediated cell-cell fusion [121].
T204 31083-31285 Sentence denotes The epitopes selected from the S glycoprotein of SARS-COV-2 can be used to design and prepare immunogenic multi-epitopic peptide vaccine against novel coronavirus disease caused by SARS-CoV-2 [122,123].
T205 31286-31432 Sentence denotes The T cell multi epitopes-based peptide vaccine was designed for COVID-19 using the envelope protein of SARS-CoV-2 as an immunogenic target [124].
T206 31433-31595 Sentence denotes Carrageenan and its structurally related compounds may serve as innovative adjuvants for enhancing peptide-based vaccine potency through immune enhancement [118].
T207 31596-31812 Sentence denotes The glycopeptides prepared by the combination of selected polysaccharides with peptides, and the peptide vaccines with polysaccharide adjuvants, will have important application prospects for inhibiting coronaviruses.
T208 31814-31880 Sentence denotes 5 Antiviral nanomaterials and delivery systems of polysaccharides
T209 31881-32015 Sentence denotes Nanobiotechnology provides a variety of solutions for the prevention, diagnosis, and treatment of infectious diseases such as viruses.
T210 32016-32151 Sentence denotes Nanoparticles can be designed as an efficient delivery system to increase the activity of low toxicity vaccines against the host [125].
T211 32152-32338 Sentence denotes The application of nanoparticles in vaccine formulations can not only improve the immunogenicity and stability of antigen, but also achieve targeted delivery and sustained release [126].
T212 32339-32449 Sentence denotes Nanomaterials may have intrinsic immunomodulatory functions, acting as adjuvants or immune potentiators [127].
T213 32450-32756 Sentence denotes The chitosan/alginate nanoparticle encapsulated bee venom (BV) with slow-releasing properties and mucosal adhesiveness has been developed, which can effectively induce non-specific immune stimulation, particularly those related to Th1 responses and viral clearance activities against PRRSV infection [128].
T214 32757-32970 Sentence denotes The effectiveness of a novel nanoparticle vaccine is supported by stimulating effective neutralizing antibody and antigen-specific T cell responses in mice immunized with a MERS-CoV nanoparticle vaccine candidate.
T215 32971-33216 Sentence denotes Using a MERS-CoV-permissive transgenic mouse model, it is shown that the mice immunized with this nanoparticle-based MERS-CoV vaccine can protect against a lethal challenge of MERS-CoV without triggering undesirable eosinophilic immunopathology.
T216 33217-33362 Sentence denotes The biocompatible hollow nanoparticle may accelerate the development of effective and safe vaccines against emerging coronavirus pathogens [129].
T217 33363-33547 Sentence denotes Bovine coronavirus (BCV) N protein-loaded chitosan nanoparticles (CNP) can significantly increase both IgA and IgG levels after the second immunization comparable to the control group.
T218 33548-33651 Sentence denotes The IgM content in serum increased after the second immunization in the BCV N protein-loaded CNP group.
T219 33652-33751 Sentence denotes These findings indicate that CNP can be used as a novel adjuvant in veterinary vaccine field [130].
T220 33752-33879 Sentence denotes In addition, the gold nanoparticles (AuNPs)-based nanomaterials also have good application prospects in anti-novel coronavirus.
T221 33880-34025 Sentence denotes An electrochemical immunosensor based on an array of AuNPs-modified carbon electrodes was used for the determination of MERS-CoV (Fig. 8 ) [131].
T222 34026-34215 Sentence denotes Highly sulfonated gold nanoparticles and heparin coated AuNPs with no cytotoxicity displayed broad-spectrum virucidal properties against HSV, HPV, RSV, dengue and lentivirus in vitro [132].
T223 34216-34349 Sentence denotes S protein plays a key role in the pathogenesis of coronavirus, and it is considered a primary target for vaccine preparation [8,133].
T224 34350-34567 Sentence denotes Virus like particles (sVLPs) were prepared by protein corona formation with IBV S protein as a model antigen and incubated with 100 nm AuNPs in a solution containing an optimized concentration of viral proteins [133].
T225 34568-34838 Sentence denotes As compared to inoculation with free proteins, vaccination with the sVLPs showed enhanced lymphatic antigen delivery, stronger antibody titers, increased splenic T-cell response, and reduced infection-associated symptoms in an avian model of coronavirus infection [133].
T226 34839-34986 Sentence denotes The study demonstrates a simple and reliable method in bridging viral antigens with synthetic nanoparticles for improved vaccine application [133].
T227 34987-35026 Sentence denotes Fig. 8 COV immunosensor array chip (a).
T228 35027-35145 Sentence denotes The immunosensor fabrication steps (b), the detection process of the competitive immunosensor for the virus (c) [131].
T229 35146-35401 Sentence denotes Additionally, polysaccharides or their derivatives, such as carrageenan oligosaccharide and fucoidan derived from marine algae with biodegradability, abundance, and non-toxicity, can be used as biocompatible reductants for green synthesis AuNPs [134,135].
T230 35402-35638 Sentence denotes Based on our previous works, we hypothesize that the S or N protein from coronavirus can be designed to be loaded onto polysaccharides capped AuNPs by protein corona formation for coronavirus nanoparticles vaccine application (Fig. 9 ).
T231 35639-35760 Sentence denotes Fig. 9 The proposed schematics illustrating the S or N protein from coronavirus loaded onto polysaccharides capped AuNPs.
T232 35762-35798 Sentence denotes 6 Conclusions & future perspectives
T233 35799-35962 Sentence denotes Polysaccharides have a long history to be used as important active ingredients in traditional Chinese medicine due to their extensive activity and reliable safety.
T234 35963-36055 Sentence denotes Polysaccharides have broad spectrum of antiviral activities and unique antiviral mechanisms.
T235 36056-36284 Sentence denotes They can exert antiviral effects by interfering with the life cycle of virus, or can indirectly exert antiviral activities by enhancing the body's immunity, which makes them have a great application prospect in anti-coronavirus.
T236 36285-36522 Sentence denotes GAGs, marine polysaccharides such as carrageenan and chitosan, traditional Chinese medicine polysaccharides such as APS and LNT, and their derivatives, have shown potent anti-coronavirus activity and multiple anti-coronavirus mechanisms.
T237 36523-36640 Sentence denotes We speculate that polysaccharides will exert anti-SARS-CoV-2 effects by the possible mechanisms as shown in Fig. 10 .
T238 36641-36792 Sentence denotes More importantly, polysaccharide-based vaccine adjuvants, nanomaterials, and drug delivery systems will play important roles in anti-coronavirus field.
T239 36793-37038 Sentence denotes Based on the immunomodulation and antiviral activity of polysaccharides, combined with nanotechnology, we put forward the strategy of loading S or N protein of coronavirus onto polysaccharide capped AuNPs vaccine for COVID-19 treatment (Fig. 9).
T240 37039-37132 Sentence denotes This review may provide a novel idea for the development of anti-COVID-19 drugs and vaccines.
T241 37133-37200 Sentence denotes Fig. 10 The proposed mechanisms of polysaccharides anti-SARS-CoV-2.