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1.
PLoS Pathog ; 18(6): e1010590, 2022 06.
Article in English | MEDLINE | ID: covidwho-1892333

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been transmitted across all over the world, in contrast to the limited epidemic of genetically- and virologically-related SARS-CoV. However, the molecular basis explaining the difference in the virological characteristics among SARS-CoV-2 and SARS-CoV has been poorly defined. Here we identified that host sialoglycans play a significant role in the efficient spread of SARS-CoV-2 infection, while this was not the case with SARS-CoV. SARS-CoV-2 infection was significantly inhibited by α2-6-linked sialic acid-containing compounds, but not by α2-3 analog, in VeroE6/TMPRSS2 cells. The α2-6-linked compound bound to SARS-CoV-2 spike S1 subunit to competitively inhibit SARS-CoV-2 attachment to cells. Enzymatic removal of cell surface sialic acids impaired the interaction between SARS-CoV-2 spike and angiotensin-converting enzyme 2 (ACE2), and suppressed the efficient spread of SARS-CoV-2 infection over time, in contrast to its least effect on SARS-CoV spread. Our study provides a novel molecular basis of SARS-CoV-2 infection which illustrates the distinctive characteristics from SARS-CoV.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Peptidyl-Dipeptidase A/metabolism , Polysaccharides/metabolism , Protein Binding , Spike Glycoprotein, Coronavirus/metabolism
3.
Anal Chem ; 94(15): 5909-5917, 2022 04 19.
Article in English | MEDLINE | ID: covidwho-1882715

ABSTRACT

SARS-CoV-2 cellular infection is mediated by the heavily glycosylated spike protein. Recombinant versions of the spike protein and the receptor-binding domain (RBD) are necessary for seropositivity assays and can potentially serve as vaccines against viral infection. RBD plays key roles in the spike protein's structure and function, and thus, comprehensive characterization of recombinant RBD is critically important for biopharmaceutical applications. Liquid chromatography coupled to mass spectrometry has been widely used to characterize post-translational modifications in proteins, including glycosylation. Most studies of RBDs were performed at the proteolytic peptide (bottom-up proteomics) or released glycan level because of the technical challenges in resolving highly heterogeneous glycans at the intact protein level. Herein, we evaluated several online separation techniques: (1) C2 reverse-phase liquid chromatography (RPLC), (2) capillary zone electrophoresis (CZE), and (3) acrylamide-based monolithic hydrophilic interaction chromatography (HILIC) to separate intact recombinant RBDs with varying combinations of glycosylations (glycoforms) for top-down mass spectrometry (MS). Within the conditions we explored, the HILIC method was superior to RPLC and CZE at separating RBD glycoforms, which differ significantly in neutral glycan groups. In addition, our top-down analysis readily captured unexpected modifications (e.g., cysteinylation and N-terminal sequence variation) and low abundance, heavily glycosylated proteoforms that may be missed by using glycopeptide data alone. The HILIC top-down MS platform holds great potential in resolving heterogeneous glycoproteins for facile comparison of biosimilars in quality control applications.


Subject(s)
Biosimilar Pharmaceuticals , COVID-19 , Chromatography, Liquid , Chromatography, Reverse-Phase/methods , Glycoproteins/chemistry , Humans , Hydrophobic and Hydrophilic Interactions , Mass Spectrometry , Polysaccharides/analysis , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/chemistry
4.
Anal Chem ; 94(15): 5776-5784, 2022 04 19.
Article in English | MEDLINE | ID: covidwho-1882709

ABSTRACT

Characterization of protein glycosylation by tandem mass spectrometry remains challenging owing to the vast diversity of oligosaccharides bound to proteins, the variation in monosaccharide linkage patterns, and the lability of the linkage between the glycan and protein. Here, we have adapted an HCD-triggered-ultraviolet photodissociation (UVPD) approach for the simultaneous localization of glycosites and full characterization of both glycan compositions and intersaccharide linkages, the latter provided by extensive cross-ring cleavages enabled by UVPD. The method is applied to study glycan compositions based on analysis of glycopeptides from proteolytic digestion of recombinant human coronaviruse spike proteins from SARS-CoV-2 and HKU1. UVPD reveals unique intersaccharide linkage information and is leveraged to localize N-linked glycoforms with confidence.


Subject(s)
COVID-19 , Viral Proteins , Glycosylation , Humans , Polysaccharides/chemistry , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Tandem Mass Spectrometry/methods , Ultraviolet Rays
5.
Biomaterials ; 286: 121585, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1881707

ABSTRACT

Among all the biological entities involved in the immune response, galectins, a family of glycan-binding proteins, have been described as key in immune cell homeostasis and modulation. More importantly, only some galectin family members are crucial in the resolution of inflammation, while others perpetuate the immune response in a pathological context. As they are expressed in most major diseases, their potential as targets for new therapies seems promising. Most of the galectin family members' ubiquitous expression points to the need for targeted treatments to ensure effectiveness. Engineered biomaterials are emerging as a promising method to improve galectin-targeted strategies' therapeutic performance. In this review, we provide an overview of the role of galectins in health and disease and their potential as therapeutic targets, as well as the state-of-the-art and future directions of galectin-targeted biomaterials.


Subject(s)
Biocompatible Materials , Galectins , Galectins/metabolism , Galectins/therapeutic use , Humans , Inflammation , Polysaccharides/metabolism
6.
Nutrients ; 14(11)2022 May 27.
Article in English | MEDLINE | ID: covidwho-1869720

ABSTRACT

Fucoidan, a sulfated polysaccharide extracted from brown seaweed, has been proposed to effectively treat and prevent various viral infections. However, the mechanisms behind its antiviral activity are not completely understood. We investigate here the global transcriptional changes in bone marrow-derived dendritic cells (BMDCs) using RNA-Seq technology. Through both analysis of differentially expressed genes (DEG) and gene set enrichment analysis (GSEA), we found that fucoidan-treated BMDCs were enriched in virus-specific response pathways, including that of SARS-CoV-2, as well as pathways associated with nucleic acid-sensing receptors (RLR, TLR, NLR, STING), and type I interferon (IFN) production. We show that these transcriptome changes are driven by well-known regulators of the inflammatory response against viruses, including IRF, NF-κB, and STAT family transcription factors. Furthermore, 435 of the 950 upregulated DEGs are classified as type I IFN-stimulated genes (ISGs). Flow cytometric analysis additionally showed that fucoidan increased MHCII, CD80, and CD40 surface markers in BMDCs, indicative of greater antigen presentation and co-stimulation functionality. Our current study suggests that fucoidan transcriptionally activates PRR signaling, type I IFN production and signaling, ISGs production, and DC maturation, highlighting a potential mechanism of fucoidan-induced antiviral activity.


Subject(s)
COVID-19 , Dendritic Cells , Antiviral Agents/metabolism , Antiviral Agents/pharmacology , Humans , Polysaccharides/metabolism , Polysaccharides/pharmacology , SARS-CoV-2
7.
Nat Commun ; 12(1): 6073, 2021 10 18.
Article in English | MEDLINE | ID: covidwho-1860369

ABSTRACT

Large-scale profiling of intact glycopeptides is critical but challenging in glycoproteomics. Data independent acquisition (DIA) is an emerging technology with deep proteome coverage and accurate quantitative capability in proteomics studies, but is still in the early stage of development in the field of glycoproteomics. We propose GproDIA, a framework for the proteome-wide characterization of intact glycopeptides from DIA data with comprehensive statistical control by a 2-dimentional false discovery rate approach and a glycoform inference algorithm, enabling accurate identification of intact glycopeptides using wide isolation windows. We further utilize a semi-empirical spectrum prediction strategy to expand the coverage of spectral libraries of glycopeptides. We benchmark our method for N-glycopeptide profiling on DIA data of yeast and human serum samples, demonstrating that DIA with GproDIA outperforms the data-dependent acquisition-based methods for glycoproteomics in terms of capacity and data completeness of identification, as well as accuracy and precision of quantification. We expect that this work can provide a powerful tool for glycoproteomic studies.


Subject(s)
Glycopeptides/analysis , Proteome/analysis , Proteomics/methods , Algorithms , Blood Proteins/chemistry , Glycoproteins/chemistry , Humans , Mass Spectrometry , Polysaccharides/chemistry , Schizosaccharomyces pombe Proteins/chemistry , Workflow
9.
Carbohydr Res ; 518: 108574, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1821162

ABSTRACT

Can envelope glycans be targeted to stop viral pandemics? Here we address this question by using molecular dynamics simulations to study the binding between 10 synthetic carbohydrate receptors (SCRs) and the 33 N-glycans most commonly found on the surfaces of enveloped viruses, including Zika virus and SARS-CoV-2. Based on association quotients derived from these simulations, we classified the SCRs as weak binders, promiscuous binders, or selective binders. The SCRs almost exclusively associate at the Man3GlcNAc2 core, which is common to all N-glycans, but the binding affinity between the SCR⋅glycan pair depends on the noncovalent interactions between the heterocycle rings and the glycan antennae. Systematic variations in the glycan and SCR structures reveal relationships that could guide the design of SCRs to attain affinity and selectivity towards a chosen envelope glycan target. With these results, envelope glycans, which are currently considered "undruggable", could become viable targets for new therapeutic strategies.


Subject(s)
COVID-19 , Receptors, Artificial , Zika Virus Infection , Zika Virus , Carbohydrates/chemistry , Humans , Molecular Dynamics Simulation , Polysaccharides/chemistry , Receptors, Artificial/chemistry , SARS-CoV-2 , Zika Virus/metabolism
10.
Carbohydr Polym ; 291: 119551, 2022 Sep 01.
Article in English | MEDLINE | ID: covidwho-1814196

ABSTRACT

As a significant public health hazard with several drug side effects during medical treatment, searching for novel therapeutic natural medicines is promising. Sulfated polysaccharides from algae, such as fucoidan, have been discovered to have a variety of medical applications, including antibacterial and immunomodulatory properties. The review emphasized on the utilization of fucoidan as an antiviral agent against viral infections by inhibiting their attachment and replication. Moreover, it can also trigger immune response against viral infection in humans. This review suggested to be use the fucoidan for the potential protective remedy against COVID-19 and addressing the antiviral activities of sulfated polysaccharide, fucoidan derived from marine algae that could be used as an anti-COVID19 drug in near future.


Subject(s)
Antiviral Agents , COVID-19 , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Humans , Polysaccharides/pharmacology , Polysaccharides/therapeutic use , Sulfates
11.
Molecules ; 27(9)2022 Apr 26.
Article in English | MEDLINE | ID: covidwho-1810050

ABSTRACT

Plant polysaccharides can increase the number and variety of beneficial bacteria in the gut and produce a variety of active substances, including short-chain fatty acids (SCFAs). Gut microbes and their specific metabolites have the effects of promoting anti-inflammatory activity, enhancing the intestinal barrier, and activating and regulating immune cells, which are beneficial for improving immunity. A strong immune system reduces inflammation caused by external viruses and other pathogens. Coronavirus disease 2019 (COVID-19) is still spreading globally, and patients with COVID-19 often have intestinal disease and weakened immune systems. This article mainly evaluates how polysaccharides in plants can improve the immune system barrier by improving the intestinal microecological balance, which may have potential in the prevention and treatment of COVID-19.


Subject(s)
COVID-19 , Gastrointestinal Microbiome , COVID-19/drug therapy , Fatty Acids, Volatile/metabolism , Humans , Immunity , Polysaccharides/metabolism , Polysaccharides/pharmacology , Polysaccharides/therapeutic use
12.
Mar Drugs ; 20(5)2022 Apr 27.
Article in English | MEDLINE | ID: covidwho-1810016

ABSTRACT

Crude polysaccharides, extracted from two seaweed species (Hizikia fusiforme and Sargassum horneri) and Haliotis discus hannai (abalone) viscera, were evaluated for their inhibitory effect against SARS-CoV-2 propagation. Plaque titration revealed that these crude polysaccharides efficiently inhibited SARS-CoV-2 propagation with IC50 values ranging from 0.35 to 4.37 µg/mL. The crude polysaccharide of H. fusiforme showed the strongest antiviral effect, with IC50 of 0.35 µg/mL, followed by S. horneri and abalone viscera with IC50 of 0.56 and 4.37 µg/mL, respectively. In addition, immunofluorescence assay, western blot, and quantitative RT-PCR analysis verified that these polysaccharides could inhibit SARS-CoV-2 replication. In Vero E6 cells, treatment with these crude polysaccharides before or after viral infection strongly inhibited the expression level of SARS-CoV-2 spikes, nucleocapsid proteins, and RNA copies of RNA-dependent RNA-polymerase and nucleocapsid. These results show that these crude marine polysaccharides effectively inhibit SARS-CoV-2 propagation by interference with viral entry.


Subject(s)
COVID-19 , Seaweed , Antiviral Agents/pharmacology , COVID-19/drug therapy , Humans , Polysaccharides/pharmacology , RNA , SARS-CoV-2 , Viscera
13.
Cell Host Microbe ; 30(6): 887-895.e4, 2022 06 08.
Article in English | MEDLINE | ID: covidwho-1763630

ABSTRACT

The SARS-CoV-2 Omicron variant harbors more than 30 mutations in the spike protein, leading to immune evasion from many therapeutic neutralizing antibodies. We reveal that a receptor-binding domain (RBD)-targeting monoclonal antibody, 35B5, exhibits potent neutralizing efficacy to Omicron. Cryo-electron microscopy structures of the extracellular domain trimer of Omicron spike with 35B5 Fab reveal that Omicron spike exhibits tight trimeric packing and high thermostability, as well as significant antigenic shifts and structural changes, within the RBD, N-terminal domain (NTD), and subdomains 1 and 2. However, these changes do not affect targeting of the invariant 35B5 epitope. 35B5 potently neutralizes SARS-CoV-2 Omicron and other variants by causing significant conformational changes within a conserved N-glycan switch that controls the transition of RBD from the "down" state to the "up" state, which allows recognition of the host entry receptor ACE2. This mode of action and potent neutralizing capacity of 35B5 indicate its potential therapeutic application for SARS-CoV-2.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , Cryoelectron Microscopy , Epitopes , Humans , Polysaccharides , Spike Glycoprotein, Coronavirus
14.
Adv Mater ; 34(21): e2200443, 2022 May.
Article in English | MEDLINE | ID: covidwho-1763176

ABSTRACT

The ongoing COVID-19 pandemic caused by SARS-CoV-2 has led to millions of deaths worldwide. Streptococcus pneumoniae (S. pneumoniae) remains a major cause of mortality in underdeveloped countries. A vaccine that prevents both SARS-CoV-2 and S. pneumoniae infection represents a long-sought "magic bullet". Herein, a nanoparticle vaccine, termed SCTV01B, is rationally developed by using the capsular polysaccharide of S. pneumoniae serotype 14 (PPS14) as the backbone to conjugate with the recombinant receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. The final formulation of conjugated nanoparticles in the network structure exhibits high thermal stability. Immunization with SCTV01B induces potent humoral and Type 1/Type 2 T helper cell (Th1/Th2) cellular immune responses in mice, rats, and rhesus macaques. In particular, SCTV01B-immunized serum not only broadly cross-neutralizes all SARS-CoV-2 variants of concern (VOCs), including the most recent Omicron variant, but also shows high opsonophagocytic activity (OPA) against S. pneumoniae serotype 14. Finally, SCTV01B vaccination confers protection against challenges with the SARS-CoV-2 mouse-adapted strain and the original strain in established murine models. Collectively, these promising preclinical results support further clinical evaluation of SCTV01B, highlighting the potency of polysaccharide-RBD-conjugated nanoparticle vaccine platforms for the development of vaccines for COVID-19 and other infectious diseases.


Subject(s)
COVID-19 , Nanoparticles , Vaccines , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Macaca mulatta/metabolism , Mice , Nanoparticles/chemistry , Pandemics , Polysaccharides , Rats , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Streptococcus pneumoniae/metabolism
15.
J Biotechnol ; 349: 32-46, 2022 Apr 10.
Article in English | MEDLINE | ID: covidwho-1757477

ABSTRACT

Over the decades, a variety of chemically synthesized drugs are being used to cure existing diseases but often these drugs could not be effectively employed for the treatment of serious and newly emerging diseases. Fortunately, in nature there occurs immense treasure of plants and microorganisms which are living jewels with respect to their richness of medically important metabolites of high value. Hence, amongst the existing microorganism(s), the marine world offers a plethora of biological entities that can contribute to alleviate numerous human ailments. Algae are one such photosynthetic microorganism found in both marine as well as fresh water which are rich source of metabolites known for their nutrient content and health benefits. Various algal species like Haematococcus, Diatoms, Griffithsia, Chlorella, Spirulina, Ulva, etc. have been identified and isolated to produce biologically active and pharmaceutically important high value compounds like astaxanthin, fucoxanthin, sulphur polysaccharides mainly galactose, rhamnose, xylose, fucose etc., which show antimicrobial, antifungal, anti-cancer, and antiviral activities. However, the production of either of these bio compounds is favored under conditions of stress. This review gives detailed information on various nutraceutical metabolites extracted from algae. Additionally focus has been made on the role of these bio compounds extracted from algae especially sulphur polysaccharides to treat several diseases with prospective treatment for SARS-CoV-2. Lastly it covers the knowledge gaps and future perspectives in this area of research.


Subject(s)
COVID-19 , Chlorella , Microalgae , COVID-19/drug therapy , Humans , Polysaccharides/chemistry , Polysaccharides/therapeutic use , Prospective Studies , SARS-CoV-2 , Sulfur
16.
Eur J Immunol ; 52(6): 946-957, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1750362

ABSTRACT

The nature of the immune responses associated with COVID-19 pathogenesis and disease severity, as well as the breadth of vaccine coverage and duration of immunity, is still unclear. Given the unpredictability for developing a severe/complicated disease, there is an urgent need in the field for predictive biomarkers of COVID-19. We have analyzed IgG Fc N-glycan traits of 82 SARS-CoV-2+ unvaccinated patients, at diagnosis, by nano-LC-ESI-MS. We determined the impact of IgG Fc glyco-variations in the induction of NK cells activation, further evaluating the association between IgG Fc N-glycans and disease severity/prognosis. We found that SARS-CoV-2+ individuals display, at diagnosis, variations in the glycans composition of circulating IgGs. Importantly, levels of galactose and sialic acid structures on IgGs are able to predict the development of a poor COVID-19 disease. Mechanistically, we demonstrated that a deficiency on galactose structures on IgG Fc in COVID-19 patients appears to induce NK cells activation associated with increased release of IFN-γ and TNF-α, which indicates the presence of pro-inflammatory immunoglobulins and higher immune activation, associated with a poor disease course. This study brings to light a novel blood biomarker based on IgG Fc glycome composition with capacity to stratify patients at diagnosis.


Subject(s)
COVID-19 , Biomarkers , COVID-19/diagnosis , COVID-19 Testing , Galactose , Glycosylation , Humans , Immunoglobulin Fc Fragments , Immunoglobulin G , Polysaccharides , SARS-CoV-2 , Severity of Illness Index
17.
Int J Biol Macromol ; 209(Pt A): 244-257, 2022 Jun 01.
Article in English | MEDLINE | ID: covidwho-1739784

ABSTRACT

Covid-19 pandemic severely affected human health worldwide. The rapidly increasing COVID-19 cases and successive mutations of the virus have made it a major challenge for scientists to find the best and efficient drug/vaccine/strategy to counteract the virus pathogenesis. As a result of research in scientific databases, regulating the immune system and its responses with nutrients and nutritional interventions is the most critical solution to prevent and combat this infection. Also, modulating other organs such as the intestine with these compounds can lead to the vaccines' effectiveness. Marine resources, mainly algae, are rich sources of nutrients and bioactive compounds with known immunomodulatory properties and the gut microbiome regulations. According to the purpose of the review, algae-derived bioactive compounds with immunomodulatory activities, sulfated polysaccharides, and polyunsaturated fatty acids have a good effect on the immune system. In addition, they have probiotic/prebiotic properties in the intestine and modulate the gut microbiomes; therefore, they can increase the effectiveness of vaccines produced. Thus, they with respectable safety, immune regulation, and modulation of microbiota have potential therapeutic against infections, especially COVID-19. They can also be employed as promising candidates for the prevention and treatment of viral infections, such as COVID-19.


Subject(s)
COVID-19 , COVID-19/drug therapy , Fatty Acids, Unsaturated/pharmacology , Fatty Acids, Unsaturated/therapeutic use , Humans , Pandemics , Polysaccharides/pharmacology , Polysaccharides/therapeutic use , Sulfates
18.
Int J Mol Sci ; 23(5)2022 Feb 25.
Article in English | MEDLINE | ID: covidwho-1736943

ABSTRACT

Rouleaux (stacked clumps) of red blood cells (RBCs) observed in the blood of COVID-19 patients in three studies call attention to the properties of several enveloped virus strains dating back to seminal findings of the 1940s. For COVID-19, key such properties are: (1) SARS-CoV-2 binds to RBCs in vitro and also in the blood of COVID-19 patients; (2) although ACE2 is its target for viral fusion and replication, SARS-CoV-2 initially attaches to sialic acid (SA) terminal moieties on host cell membranes via glycans on its spike protein; (3) certain enveloped viruses express hemagglutinin esterase (HE), an enzyme that releases these glycan-mediated bindings to host cells, which is expressed among betacoronaviruses in the common cold strains but not the virulent strains, SARS-CoV, SARS-CoV-2 and MERS. The arrangement and chemical composition of the glycans at the 22 N-glycosylation sites of SARS-CoV-2 spike protein and those at the sialoglycoprotein coating of RBCs allow exploration of specifics as to how virally induced RBC clumping may form. The in vitro and clinical testing of these possibilities can be sharpened by the incorporation of an existing anti-COVID-19 therapeutic that has been found in silico to competitively bind to multiple glycans on SARS-CoV-2 spike protein.


Subject(s)
COVID-19/metabolism , Erythrocytes/metabolism , SARS-CoV-2/metabolism , Sialoglycoproteins/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Basigin/metabolism , Binding Sites , COVID-19/virology , Glycosylation , Hemagglutination , Hemagglutinins, Viral/metabolism , Humans , N-Acetylneuraminic Acid/metabolism , Polysaccharides/metabolism , Protein Binding , SARS-CoV-2/physiology , Viral Fusion Proteins/metabolism , Virus Internalization
20.
Molecules ; 27(5)2022 Mar 01.
Article in English | MEDLINE | ID: covidwho-1715569

ABSTRACT

COVID-19 is an endothelial disease. All the major comorbidities that increase the risk for severe SARS-CoV-2 infection and severe COVID-19 including old age, obesity, diabetes, hypertension, respiratory disease, compromised immune system, coronary artery disease or heart failure are associated with dysfunctional endothelium. Genetics and environmental factors (epigenetics) are major risk factors for endothelial dysfunction. Individuals with metabolic syndrome are at increased risk for severe SARS-CoV-2 infection and poor COVID-19 outcomes and higher risk of mortality. Old age is a non-modifiable risk factor. All other risk factors are modifiable. This review also identifies dietary risk factors for endothelial dysfunction. Potential dietary preventions that address endothelial dysfunction and its sequelae may have an important role in preventing SARS-CoV-2 infection severity and are key factors for future research to address. This review presents some dietary bioactives with demonstrated efficacy against dysfunctional endothelial cells. This review also covers dietary bioactives with efficacy against SARS-CoV-2 infection. Dietary bioactive compounds that prevent endothelial dysfunction and its sequelae, especially in the gastrointestinal tract, will result in more effective prevention of SARS-CoV-2 variant infection severity and are key factors for future food research to address.


Subject(s)
Endothelium/drug effects , Flavonoids/pharmacology , Functional Food/analysis , SARS-CoV-2/drug effects , COVID-19/drug therapy , COVID-19/pathology , COVID-19/virology , Endothelium/metabolism , Flavonoids/metabolism , Flavonoids/therapeutic use , Humans , Polysaccharides/pharmacology , Polysaccharides/therapeutic use , Risk Factors , SARS-CoV-2/isolation & purification , Stilbenes/pharmacology , Stilbenes/therapeutic use , Terpenes/pharmacology , Terpenes/therapeutic use
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