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1.
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
2.
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
3.
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
4.
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
5.
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
6.
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
7.
Viruses ; 14(2)2022 02 18.
Article in English | MEDLINE | ID: covidwho-1707748

ABSTRACT

In the current context of the COVID-19 pandemic, it appears that our scientific resources and the medical community are not sufficiently developed to combat rapid viral spread all over the world. A number of viruses causing epidemics have already disseminated across the world in the last few years, such as the dengue or chinkungunya virus, the Ebola virus, and other coronavirus families such as Middle East respiratory syndrome (MERS-CoV) and severe acute respiratory syndrome (SARS-CoV). The outbreaks of these infectious diseases have demonstrated the difficulty of treating an epidemic before the creation of vaccine. Different antiviral drugs already exist. However, several of them cause side effects or have lost their efficiency because of virus mutations. It is essential to develop new antiviral strategies, but ones that rely on more natural compounds to decrease the secondary effects. Polysaccharides, which have come to be known in recent years for their medicinal properties, including antiviral activities, are an excellent alternative. They are essential for the metabolism of plants, microorganisms, and animals, and are directly extractible. Polysaccharides have attracted more and more attention due to their therapeutic properties, low toxicity, and availability, and seem to be attractive candidates as antiviral drugs of tomorrow.


Subject(s)
Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Polysaccharides/chemistry , Polysaccharides/pharmacology , Viruses/drug effects , Animals , Disease Outbreaks/prevention & control , Ebolavirus/drug effects , Humans , SARS-CoV-2/drug effects , Virus Diseases/drug therapy , Virus Replication/drug effects , Viruses/classification , Viruses/pathogenicity
8.
Mar Drugs ; 20(2)2022 Jan 24.
Article in English | MEDLINE | ID: covidwho-1707249

ABSTRACT

Fucoidan is a polysaccharide obtained from marine brown algae, with anti-inflammatory, anti-viral, and immune-enhancing properties, thus, fucoidan may be used as an alternative treatment (complementary to prescribed medical therapy) for COVID-19 recovery. This work aimed to determine the ex-vivo effects of treatment with fucoidan (20 µg/mL) on mitochondrial membrane potential (ΔΨm, using a cationic cyanine dye, 3,3'-dihexyloxacarbocyanine iodide (DiOC6(3)) on human peripheral blood mononuclear cells (HPBMC) isolated from healthy control (HC) subjects, COVID-19 patients (C-19), and subjects that recently recovered from COVID-19 (R1, 40 ± 13 days after infection). In addition, ex-vivo treatment with fucoidan (20 and 50 µg/mL) was evaluated on ΔΨm loss induced by carbonyl cyanide 3-chlorophenylhydrazone (CCCP, 150 µM) in HPBMC isolated from healthy subjects (H) and recovered subjects at 11 months post-COVID-19 (R2, 335 ± 20 days after infection). Data indicate that SARS-CoV-2 infection induces HPBMC loss of ΔΨm, even 11 months after infection, however, fucoidan promotes recovery of ΔΨm in PBMCs from COVID-19 recovered subjects. Therefore, fucoidan may be a potential treatment to diminish long-term sequelae from COVID-19, using mitochondria as a therapeutic target for the recovery of cellular homeostasis.


Subject(s)
COVID-19 , Leukocytes, Mononuclear/drug effects , Membrane Potential, Mitochondrial/drug effects , Polysaccharides/pharmacology , SARS-CoV-2 , Adult , Aged , Female , Humans , Leukocytes, Mononuclear/physiology , Male , Middle Aged , Mitochondria/drug effects , Phaeophyta/chemistry , Polysaccharides/chemistry , Young Adult
9.
Carbohydr Polym ; 280: 119006, 2022 Mar 15.
Article in English | MEDLINE | ID: covidwho-1588175

ABSTRACT

Caulerpa lentillifera (Bryopsidophyceae, Chlorophyta) is an edible seaweed attracting great attention for its expansion of farming scale and increasing consumption in these years. In the present study, a sulfated polysaccharide (CLSP-2) was isolated and separated from C. lentillifera, and its chemical structure was elucidated by a series of chemical and spectroscopic methods. Among these methods, mild acid hydrolysis and photocatalytic degradation were applied to release mono- and oligo-saccharide fragments which were further identified by HPLC-MSn analysis, affording the information of the sugar sequences and the sulfate substitution in CLSP-2. Results indicated that the backbone of CLSP-2 was constructed of →6)-ß-Manp-(1→ with sulfated branches at C2, which were comprised of prevalent →3)-ß-Galp4S-(1→, →3)-ß-Galp2,4S-(1→, and minor Xyl. In addition, the virus neutralization assay revealed that CLSP-2 could effectively protect HeLa cells against SARS-CoV-2 infection with an IC50 of 48.48 µg/mL. Hence, the present study suggests CLSP-2 as a promising agent against SARS-CoV-2.


Subject(s)
COVID-19/virology , Caulerpa/chemistry , Polysaccharides/chemistry , Polysaccharides/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Chromatography, High Pressure Liquid/methods , HeLa Cells , Humans , Hydrolysis , Magnetic Resonance Spectroscopy/methods , Mass Spectrometry/methods , Molecular Weight , Polysaccharides/analysis , SARS-CoV-2 , Seaweed/chemistry , Spectroscopy, Fourier Transform Infrared/methods , Sulfates/chemistry
10.
Viruses ; 14(1)2021 12 24.
Article in English | MEDLINE | ID: covidwho-1580407

ABSTRACT

Only a mere fraction of the huge variety of human pathogenic viruses can be targeted by the currently available spectrum of antiviral drugs. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak has highlighted the urgent need for molecules that can be deployed quickly to treat novel, developing or re-emerging viral infections. Sulfated polysaccharides are found on the surfaces of both the susceptible host cells and the majority of human viruses, and thus can play an important role during viral infection. Such polysaccharides widely occurring in natural sources, specifically those converted into sulfated varieties, have already proved to possess a high level and sometimes also broad-spectrum antiviral activity. This antiviral potency can be determined through multifold molecular pathways, which in many cases have low profiles of cytotoxicity. Consequently, several new polysaccharide-derived drugs are currently being investigated in clinical settings. We reviewed the present status of research on sulfated polysaccharide-based antiviral agents, their structural characteristics, structure-activity relationships, and the potential of clinical application. Furthermore, the molecular mechanisms of sulfated polysaccharides involved in viral infection or in antiviral activity, respectively, are discussed, together with a focus on the emerging methodology contributing to polysaccharide-based drug development.


Subject(s)
Antiviral Agents/pharmacology , Biological Products/pharmacology , COVID-19/epidemiology , Polysaccharides/pharmacology , Viruses/drug effects , Antiviral Agents/chemical synthesis , Antiviral Agents/chemistry , Biological Products/chemical synthesis , Biological Products/chemistry , COVID-19/drug therapy , Heparin/chemical synthesis , Heparin/chemistry , Heparin/pharmacology , Humans , Polysaccharides/chemistry , SARS-CoV-2/drug effects , Structure-Activity Relationship , Sulfates/chemistry , Sulfates/pharmacology , Virus Diseases/drug therapy , Virus Internalization/drug effects , Viruses/pathogenicity
11.
Int J Mol Sci ; 22(24)2021 Dec 08.
Article in English | MEDLINE | ID: covidwho-1554850

ABSTRACT

The COVID-19 pandemic continues to spread around the world and remains a major public health threat. Vaccine inefficiency, vaccination breakthroughs and lack of supply, especially in developing countries, as well as the fact that a non-negligible part of the population either refuse vaccination or cannot be vaccinated due to age, pre-existing illness or non-response to existing vaccines intensify this issue. This might also contribute to the emergence of new variants, being more efficiently transmitted, more virulent and more capable of escaping naturally acquired and vaccine-induced immunity. Hence, the need of effective and viable prevention options to reduce viral transmission is of outmost importance. In this study, we investigated the antiviral effect of iota-, lambda- and kappa-carrageenan, sulfated polysaccharides extracted from red seaweed, on SARS-CoV-2 Wuhan type and the spreading variants of concern (VOCs) Alpha, Beta, Gamma and Delta. Carrageenans as part of broadly used nasal and mouth sprays as well as lozenges have the potential of first line defense to inhibit the infection and transmission of SARS-CoV-2. Here, we demonstrate by using a SARS-CoV-2 spike pseudotyped lentivirus particles (SSPL) system and patient-isolated SARS-CoV-2 VOCs to infect transgenic A549ACE2/TMPRSS2 and Calu-3 human lung cells that all three carrageenan types exert antiviral activity. Iota-carrageenan exhibits antiviral activity with comparable IC50 values against the SARS-CoV-2 Wuhan type and the VOCs. Altogether, these results indicate that iota-carrageenan might be effective for prophylaxis and treatment of SARS-CoV-2 infections independent of the present and potentially future variants.


Subject(s)
COVID-19/drug therapy , COVID-19/virology , Carrageenan/pharmacology , SARS-CoV-2/drug effects , Virus Replication/drug effects , Animals , Antiviral Agents/pharmacology , COVID-19/epidemiology , COVID-19/immunology , COVID-19 Vaccines/pharmacology , Chlorocebus aethiops , HEK293 Cells , Humans , Pandemics , Polysaccharides/pharmacology , SARS-CoV-2/metabolism , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/immunology , Vaccination/methods , Vero Cells
12.
Carbohydr Polym ; 285: 118971, 2022 Jun 01.
Article in English | MEDLINE | ID: covidwho-1549670

ABSTRACT

Ligusticum chuanxiong, the dried rhizome of Ligusticum chuanxiong Hort, has been widely applied in traditional Chinese medicine for treating plague, and it has appeared frequently in the prescriptions against COVID-19 lately. Ligusticum chuanxiong polysaccharide (LCPs) is one of the effective substances, which has various activities, such as, anti-oxidation, promoting immunity, anti-tumor, and anti-bacteria. The purified fractions of LCPs are considered to be pectic polysaccharides, which are mainly composed of GalA, Gal, Ara and Rha, and are generally linked by α-1,4-d-GalpA, α-1,2-l-Rhap, α-1,5-l-Araf, ß-1,3-d-Galp and ß-1,4-d-Galp, etc. The pectic polysaccharide shows an anti-infective inflammatory activity, which is related to antiviral infection of Ligusticum chuanxiong. In this article, the isolation, purification, structural features, and biological activities of LCPs in recent years are reviewed, and the potential of LCPs against viral infection as well as questions that need future research are discussed.


Subject(s)
COVID-19/drug therapy , Ligusticum/chemistry , Polysaccharides/chemistry , Polysaccharides/pharmacology , Adjuvants, Immunologic/pharmacology , Adjuvants, Immunologic/therapeutic use , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Antioxidants/pharmacology , Antioxidants/therapeutic use , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/virology , Carbohydrate Conformation , Carbohydrate Sequence , Drugs, Chinese Herbal , Humans , Polysaccharides/isolation & purification , SARS-CoV-2/drug effects , SARS-CoV-2/isolation & purification
13.
Future Microbiol ; 16: 1289-1301, 2021 11.
Article in English | MEDLINE | ID: covidwho-1484978

ABSTRACT

COVID-19, caused by the SARS-CoV-2 outbreak, has resulted in a massive global health crisis. Bioactive molecules extracted or synthesized using starting material obtained from marine species, including griffithsin, plitidepsin and fingolimod are in clinical trials to evaluate their anti-SARS-CoV-2 and anti-HIV efficacies. The current review highlights the anti-SARS-CoV-2 potential of marine-derived phytochemicals explored using in silico, in vitro and in vivo models. The current literature suggests that these molecules have the potential to bind with various key drug targets of SARS-CoV-2. In addition, many of these agents have anti-inflammatory and immunomodulatory potentials and thus could play a role in the attenuation of COVID-19 complications. Overall, these agents may play a role in the management of COVID-19, but further preclinical and clinical studies are still required to establish their role in the mitigation of the current viral pandemic.


Subject(s)
Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Oceans and Seas , SARS-CoV-2/drug effects , Alkaloids/pharmacology , Anti-Inflammatory Agents , Antiviral Agents/chemistry , Depsipeptides , Fingolimod Hydrochloride/chemistry , Fingolimod Hydrochloride/pharmacology , Humans , Lectins , Marine Biology , Molecular Docking Simulation , Peptides, Cyclic/chemistry , Peptides, Cyclic/pharmacology , Phycocyanin/pharmacology , Phytochemicals , Plant Lectins/chemistry , Plant Lectins/pharmacology , Polyphenols/pharmacology , Polysaccharides/pharmacology , Seaweed , Sesquiterpenes/pharmacology
14.
Viruses ; 13(9)2021 09 13.
Article in English | MEDLINE | ID: covidwho-1411081

ABSTRACT

Over the decades, the world has witnessed diverse virus associated pandemics. The significant inhibitory effects of marine sulfated polysaccharides against SARS-CoV-2 shows its therapeutic potential in future biomedical applications and drug development. Algal polysaccharides exhibited significant role in antimicrobial, antitumor, antioxidative, antiviral, anticoagulant, antihepatotoxic and immunomodulating activities. Owing to their health benefits, the sulfated polysaccharides from marine algae are a great deal of interest globally. Algal polysaccharides such as agar, alginate, carrageenans, porphyran, fucoidan, laminaran and ulvans are investigated for their nutraceutical potential at different stages of infection processes, structural diversity, complexity and mechanism of action. In this review, we focus on the recent antiviral studies of the marine algae-based polysaccharides and their potential towards antiviral medicines.


Subject(s)
Antiviral Agents/pharmacology , Aquatic Organisms/chemistry , Polysaccharides/pharmacology , Seaweed/chemistry , Virus Diseases/epidemiology , Alginates/chemistry , Alginates/pharmacology , Antiviral Agents/chemistry , Glucans/chemistry , Glucans/pharmacology , Humans , Molecular Structure , Pandemics , Polysaccharides/chemistry , Virus Diseases/drug therapy , Virus Diseases/etiology , Virus Diseases/prevention & control
15.
Mar Drugs ; 19(1)2020 Dec 24.
Article in English | MEDLINE | ID: covidwho-1389434

ABSTRACT

Compromised lung function is a feature of both infection driven and non-infective pathologies. Viral infections-including the current pandemic strain SARS-CoV-2-that affect lung function can cause both acute and long-term chronic damage. SARS-CoV-2 infection suppresses innate immunity and promotes an inflammatory response. Targeting these aspects of SARS-CoV-2 is important as the pandemic affects greater proportions of the population. In clinical and animal studies, fucoidans have been shown to increase innate immunity and decrease inflammation. In addition, dietary fucoidan has been shown to attenuate pulmonary damage in a model of acute viral infection. Direct inhibition of SARS-CoV-2 in vitro has been described, but is not universal. This short review summarizes the current research on fucoidan with regard to viral lung infections and lung damage.


Subject(s)
COVID-19/drug therapy , Lung/drug effects , Polysaccharides/pharmacology , SARS-CoV-2 , Animals , COVID-19/immunology , Humans , Lung/physiology , Lung Diseases/drug therapy , Polysaccharides/therapeutic use , Virus Diseases/drug therapy
16.
Appl Biochem Biotechnol ; 194(2): 671-693, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1375835

ABSTRACT

The growth of respiratory diseases, as witnessed through the SARS and COVID-19 outbreaks, and antimicrobial-resistance together pose a serious threat to humanity. One reason for antimicrobial resistance is formation of bacterial biofilms. In this study the sulphated polysaccharides from green algae Chlamydomonas reinhardtii (Cr-SPs) is tested for its antibacterial and antibiofilm potential against Klebsiella pneumoniae and Serratia marcescens. Agar cup assay clearly indicated the antibacterial potential of Cr-SPs. Minimum inhibitory concentration (MIC50) of Cr-SPs against Klebsiella pneumoniae was found to be 850 µg/ml, and it is 800 µg/ml in Serratia marcescens. Time-kill and colony-forming ability assays suggest the concentration-dependent bactericidal potential of Cr-SPs. Cr-SPs showed 74-100% decrease in biofilm formation in a concentration-dependent manner by modifying the cell surface hydrophobic properties of these bacteria. Cr-SPs have also distorted preformed-biofilms by their ability to interact and destroy the extra polymeric substance and eDNA of the matured biofilm. Scanning electron microscopy analysis showed that Cr-SPs effectively altered the morphology of these bacterial cells and distorted the bacterial biofilms. Furthermore reduced protease, urease and prodigiosin pigment production suggest that Cr-SPs interferes the quorum sensing mechanism in these bacteria. The current study paves way towards developing Cr-SPs as a control strategy for treatment of respiratory tract infections.


Subject(s)
Biofilms/drug effects , Polysaccharides/pharmacology , Quorum Sensing/drug effects , Respiratory Tract Infections/drug therapy , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Biofilms/growth & development , COVID-19/drug therapy , COVID-19/virology , Chlorophyta/chemistry , Humans , Klebsiella pneumoniae/growth & development , Klebsiella pneumoniae/pathogenicity , Microbial Sensitivity Tests , Polysaccharides/chemistry , Respiratory Tract Infections/microbiology , SARS-CoV-2/drug effects , Serratia marcescens/growth & development , Serratia marcescens/pathogenicity
17.
Nat Prod Res ; 34(16): 2249-2254, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-1343564

ABSTRACT

The enhanced osteoblast differentiation is beneficial to the prevention of osteoporosis. In this study, a homogeneous polysaccharide (LRP-S2A) with the potential of promoting osteoblast differentiation was obtained from the fruits of Lycium ruthenicum, a traditional herb for treatment of postmenopausal metabolic disorders. Structural identification indicated that LRP-S2A, with a relative molecular weight of 2.65 × 106 Da and an uronic acid content of 41.8%, contained Rha, Ara, Gal, Glc and GlcA in a molar ratio of 1.00 : 2.07 : 0.57 : 2.59 : 4.33 and was composed of a backbone consisting of 6-O-Me-α-(1→4)-D-GlcpA, 2-O-acetyl-α-(1→4)-D-Glcp, α-(1→2,4)-L-Rhap, ß-(1→3)-D-Galp andα-(1→3,5)-L-Araf, and some branches consisting of 6-O-Me-α-(1→4)-D-GlcpA and terminal α-L-Araf. These results suggested that LRP-S2A with the potential of promoting osteoblast differentiation was a new acidic polysaccharide.


Subject(s)
Cell Differentiation/drug effects , Lycium/chemistry , Osteoblasts/cytology , Polysaccharides/chemistry , Animals , Cells, Cultured , Fruit/chemistry , Humans , Molecular Weight , Polysaccharides/pharmacology , Uronic Acids/analysis
18.
Mar Drugs ; 19(8)2021 Jul 26.
Article in English | MEDLINE | ID: covidwho-1325731

ABSTRACT

Over 182 million confirmed cases of COVID-19 and more than 4 million deaths have been reported to date around the world. It is essential to identify broad-spectrum antiviral agents that may prevent or treat infections by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) but also by other coronaviruses that may jump the species barrier in the future. We evaluated the antiviral selectivity of griffithsin and sulfated and non-sulfated polysaccharides against SARS-CoV-1 and SARS-CoV-2 using a cytotoxicity assay and a cell-based pseudoviral model. The half-maximal cytotoxic concentration (CC50) and half-maximal effective concentration (EC50) were determined for each compound, using a dose-response-inhibition analysis on GraphPad Prism v9.0.2 software (San Diego, CA, USA). The therapeutic index (TI = CC50/EC50) was calculated for each compound. The potential synergistic, additive, or antagonistic effect of different compound combinations was determined by CalcuSyn v1 software (Biosoft, Cambridge, UK), which estimated the combination index (CI) values. Iota and lambda carrageenan showed the most potent antiviral activity (EC50 between 3.2 and 7.5 µg/mL). Carrageenan and griffithsin combinations exhibited synergistic activity (EC50 between 0.2 and 3.8 µg/mL; combination index <1), including against recent SARS-CoV-2 mutations. The griffithsin and carrageenan combination is a promising candidate to prevent or treat infections by SARS-CoV-1 and SARS-CoV-2.


Subject(s)
Antiviral Agents/pharmacology , Carrageenan/pharmacology , Plant Lectins/pharmacology , SARS Virus/drug effects , SARS-CoV-2/drug effects , COVID-19/drug therapy , COVID-19/virology , Drug Synergism , HeLa Cells , Humans , Models, Biological , Polysaccharides/pharmacology
19.
Mar Drugs ; 19(8)2021 Jul 22.
Article in English | MEDLINE | ID: covidwho-1325729

ABSTRACT

SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) is a novel coronavirus strain that emerged at the end of 2019, causing millions of deaths so far. Despite enormous efforts being made through various drug discovery campaigns, there is still a desperate need for treatments with high efficacy and selectivity. Recently, marine sulfated polysaccharides (MSPs) have earned significant attention and are widely examined against many viral infections. This article attempted to produce a comprehensive report about MSPs from different marine sources alongside their antiviral effects against various viral species covering the last 25 years of research articles. Additionally, these reported MSPs were subjected to molecular docking and dynamic simulation experiments to ascertain potential interactions with both the receptor-binding domain (RBD) of SARS CoV-2's spike protein (S-protein) and human angiotensin-converting enzyme-2 (ACE2). The possible binding sites on both S-protein's RBD and ACE2 were determined based on how they bind to heparin, which has been reported to exhibit significant antiviral activity against SARS CoV-2 through binding to RBD, preventing the virus from affecting ACE2. Moreover, our modeling results illustrate that heparin can also bind to and block ACE2, acting as a competitor and protective agent against SARS CoV-2 infection. Nine of the investigated MSPs candidates exhibited promising results, taking into consideration the newly emerged SARS CoV-2 variants, of which five were not previously reported to exert antiviral activity against SARS CoV-2, including sulfated galactofucan (1), sulfated polymannuroguluronate (SPMG) (2), sulfated mannan (3), sulfated heterorhamnan (8), and chondroitin sulfate E (CS-E) (9). These results shed light on the importance of sulfated polysaccharides as potential SARS-CoV-2 inhibitors.


Subject(s)
Antiviral Agents/pharmacology , Aquatic Organisms/chemistry , Polysaccharides/pharmacology , SARS-CoV-2/chemistry , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/metabolism , Antiviral Agents/chemistry , Binding Sites , Computer Simulation , Heparin/chemistry , Heparin/metabolism , Humans , Molecular Docking Simulation , Polysaccharides/chemistry , Protein Binding , SARS-CoV-2/genetics , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism , Structure-Activity Relationship , Sulfates/chemistry
20.
Molecules ; 26(9)2021 Apr 29.
Article in English | MEDLINE | ID: covidwho-1217102

ABSTRACT

Hemostasis disorders play an important role in the pathogenesis, clinical manifestations, and outcome of COVID-19. First of all, the hemostasis system suffers due to a complicated and severe course of COVID-19. A significant number of COVID-19 patients develop signs of hypercoagulability, thrombocytopenia, and hyperfibrinolysis. Patients with severe COVID-19 have a tendency toward thrombotic complications in the venous and arterial systems, which is the leading cause of death in this disease. Despite the success achieved in the treatment of SARS-CoV-2, the search for new effective anticoagulants, thrombolytics, and fibrinolytics, as well as their optimal dose strategies, continues to be relevant. The wide therapeutic potential of seaweed sulfated polysaccharides (PSs), including anticoagulant, thrombolytic, and fibrinolytic activities, opens up new possibilities for their study in experimental and clinical trials. These natural compounds can be important complementary drugs for the recovery from hemostasis disorders due to their natural origin, safety, and low cost compared to synthetic drugs. In this review, the authors analyze possible pathophysiological mechanisms involved in the hemostasis disorders observed in the pathological progression of COVID-19, and also focus the attention of researchers on seaweed PSs as potential drugs aimed to correction these disorders in COVID-19 patients. Modern literature data on the anticoagulant, antithrombotic, and fibrinolytic activities of seaweed PSs are presented, depending on their structural features (content and position of sulfate groups on the main chain of PSs, molecular weight, monosaccharide composition and type of glycosidic bonds, the degree of PS chain branching, etc.). The mechanisms of PS action on the hemostasis system and the issues of oral bioavailability of PSs, important for their clinical use as oral anticoagulant and antithrombotic agents, are considered. The combination of the anticoagulant, thrombolytic, and fibrinolytic properties, along with low toxicity and relative cheapness of production, open up prospects for the clinical use of PSs as alternative sources of new anticoagulant and antithrombotic compounds. However, further investigation and clinical trials are needed to confirm their efficacy.


Subject(s)
Anticoagulants/pharmacology , COVID-19/complications , Hemostasis/drug effects , Polysaccharides/pharmacology , Seaweed , Sulfates/pharmacology , Thrombosis/complications , Animals , Anticoagulants/chemistry , Anticoagulants/pharmacokinetics , Anticoagulants/therapeutic use , COVID-19/blood , COVID-19/drug therapy , Drug Discovery , Humans , Polysaccharides/chemistry , Polysaccharides/pharmacokinetics , Polysaccharides/therapeutic use , Seaweed/chemistry , Sulfates/chemistry , Sulfates/pharmacokinetics , Sulfates/therapeutic use , Thrombosis/blood , Thrombosis/drug therapy
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