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1.
Int J Biol Macromol ; 238: 124168, 2023 May 31.
Article Dans Anglais | MEDLINE | ID: covidwho-2271375

Résumé

The structure of the sulfated galactan from the red alga Botryocladia occidentalis (BoSG) was originally proposed as a simple repeating disaccharide of alternating 4-linked α-galactopyranose (Galp) and 3-linked ß-Galp units with variable sulfation pattern. Abundance was estimated only for the α-Galp units: one-third of 2,3-disulfation and one-third of 2-monosulfation. Here, we isolated again the same BoSG fractions from the anion-exchange chromatography, obtaining the same NMR profile of the first report. More careful NMR analysis led us to revise the structure. A more complex sulfation pattern was noted along with the occurrence of 4-linked α-3,6-anhydro-Galp (AnGalp) units. Interestingly, the more sulfated BoSG fraction showed slightly reduced in vitro anti-SARS-CoV-2 activities against both wild-type and delta variants, and significantly reduced anticoagulant activity. The BoSG fractions showed no cytotoxic effects. The reduction in both bioactivities is attributed to the presence of the AnGalp unit. Docking scores from computational simulations using BoSG disaccharide constructs on wild-type and delta S-proteins, and binding analysis through competitive SPR assays using blood (co)-factors (antithrombin, heparin cofactor II and thrombin) and four S-proteins (wild-type, delta, gamma, and omicron) strongly support the conclusion about the deleterious impact of the AnGalp unit.


Sujets)
COVID-19 , Rhodophyta , Humains , Galactanes/pharmacologie , Galactanes/composition chimique , Sulfates/composition chimique , SARS-CoV-2 , Anticoagulants/pharmacologie , Anticoagulants/composition chimique , Rhodophyta/composition chimique , Diholoside/pharmacologie
2.
Carbohydr Polym ; 299: 120173, 2023 Jan 01.
Article Dans Anglais | MEDLINE | ID: covidwho-2240925

Résumé

COVID-19 caused by SARS-CoV-2 has spread around the world at an unprecedented rate. A more homogeneous oligo-porphyran with mean molecular weight of 2.1 kD, named OP145, was separated from Pyropia yezoensis. NMR analysis showed OP145 was mainly composed of →3)-ß-d-Gal-(1 â†’ 4)-α-l-Gal (6S) repeating units with few replacement of 3,6-anhydride, and the molar ratio was 1:0.85:0.11. MALDI-TOF MS revealed OP145 contained mainly tetrasulfate-oligogalactan with Dp range from 4 to 10 and with no more than two 3,6-anhydro-α-l-Gal replacement. The inhibitory activity of OP145 against SARS-CoV-2 was investigated in vitro and in silico. OP145 could bind to Spike glycoprotein (S-protein) through SPR result, and pseudovirus tests confirmed that OP145 could inhibite the infection with an EC50 of 37.52 µg/mL. Molecular docking simulated the interaction between the main component of OP145 and S-protein. All the results indicated that OP145 had the potency to treat and prevent COVID-19.


Sujets)
Antiviraux , COVID-19 , SARS-CoV-2 , Humains , Simulation de docking moléculaire , SARS-CoV-2/effets des médicaments et des substances chimiques , Spectrométrie de masse MALDI , Sulfates , Antiviraux/pharmacologie , Rhodophyta/composition chimique
3.
J Biol Chem ; 298(5): 101856, 2022 05.
Article Dans Anglais | MEDLINE | ID: covidwho-1814630

Résumé

Sulfation pattern and molecular weight (MW) play a key role in the biological actions of sulfated glycans. Besides anticoagulant effects, certain sulfated glycans can also exhibit anti-SARS-CoV-2 properties. To develop a more selective antiviral carbohydrate, an efficient strategy to separate these two actions is required. In this work, low MW fractions derived from the red alga Botryocladia occidentalis sulfated galactan (BoSG) were generated, structurally characterized, and tested for activity against SARS-CoV-2 and blood coagulation. The lowest MW fraction was found to be primarily composed of octasaccharides of monosulfated monosaccharides. Unlike heparin or native BoSG, we found that hydrolyzed BoSG products had weak anticoagulant activities as seen by aPTT and inhibitory assays using purified cofactors. In contrast, lower MW BoSG-derivatives retained anti-SARS-CoV-2 activity using SARS-CoV-2 spike (S)-protein pseudotyped lentivirus vector in HEK-293T-hACE2 cells monitored by GFP. Surface plasmon resonance confirmed that longer chains are necessary for BoSG to interact with coagulation cofactors but is not required for interactions with certain S-protein variants. We observed distinct affinities of BoSG derivatives for the S-proteins of different SARS-CoV-2 strains, including WT, N501Y (Alpha), K417T/E484K/N501Y (Gamma), and L542R (Delta) mutants, and stronger affinity for the N501Y-containing variants. Docking of the four possible monosulfated BoSG disaccharides in interactions with the N501Y mutant S-protein predicted potential binding poses of the BoSG constructs and favorable binding in close proximity to the 501Y residue. Our results demonstrate that depolymerization and fractionation of BoSG are an effective strategy to segregate its anticoagulant property from its anti-SARS-CoV-2 action.


Sujets)
Anticoagulants , Antiviraux , Galactanes , Rhodophyta , SARS-CoV-2 , Anticoagulants/composition chimique , Anticoagulants/pharmacologie , Antiviraux/composition chimique , Antiviraux/pharmacologie , COVID-19 , Galactanes/composition chimique , Galactanes/pharmacologie , Cellules HEK293 , Humains , Rhodophyta/composition chimique , SARS-CoV-2/effets des médicaments et des substances chimiques , Glycoprotéine de spicule des coronavirus/composition chimique , Sulfates/composition chimique
4.
Carbohydr Res ; 505: 108326, 2021 Jul.
Article Dans Anglais | MEDLINE | ID: covidwho-1213065

Résumé

The viral infection caused by SARS-CoV-2 has increased the mortality rate and engaged several adverse effects on the affected individuals. Currently available antiviral drugs have found to be unsuccessful in the treatment of COVID-19 patients. The demand for efficient antiviral drugs has created a huge burden on physicians and health workers. Plasma therapy seems to be less accomplishable due to insufficient donors to donate plasma and low recovery rate from viral infection. Repurposing of antivirals has been evolved as a suitable strategy in the current treatment and preventive measures. The concept of drug repurposing represents new experimental approaches for effective therapeutic benefits. Besides, SARS-CoV-2 exhibits several complications such as lung damage, blood clot formation, respiratory illness and organ failures in most of the patients. Based on the accumulation of data, sulfated marine polysaccharides have exerted successful inhibition of virus entry, attachment and replication with known or unknown possible mechanisms against deadly animal and human viruses so far. Since the virus entry into the host cells is the key process, the prevention of such entry mechanism makes any antiviral strategy effective. Enveloped viruses are more sensitive to polyanions than non-enveloped viruses. Besides, the viral infection caused by RNA virus types embarks severe oxidative stress in the human body that leads to malfunction of tissues and organs. In this context, polysaccharides play a very significant role in providing shielding effect against the virus due to their polyanionic rich features and a molecular weight that hinders their reactive surface glycoproteins. Significantly the functional groups especially sulfate, sulfate pattern and addition, uronic acids, monosaccharides, glycosidic linkage and high molecular weight have greater influence in the antiviral activity. Moreover, they are very good antioxidants that can reduce the free radical generation and provokes intracellular antioxidant enzymes. Additionally, polysaccharides enable a host-virus immune response, activate phagocytosis and stimulate interferon systems. Therefore, polysaccharides can be used as candidate drugs, adjuvants in vaccines or combination with other antivirals, antioxidants and immune-activating nutritional supplements and antiviral materials in healthcare products to prevent SARS-CoV-2 infection.


Sujets)
Anticoagulants/usage thérapeutique , Antiviraux/usage thérapeutique , , Facteurs immunologiques/usage thérapeutique , Polyosides/usage thérapeutique , Embolie pulmonaire/traitement médicamenteux , Insuffisance respiratoire/traitement médicamenteux , Anticoagulants/composition chimique , Anticoagulants/isolement et purification , Antiviraux/composition chimique , Antiviraux/isolement et purification , Plaquettes/effets des médicaments et des substances chimiques , Plaquettes/anatomopathologie , Plaquettes/virologie , COVID-19/complications , COVID-19/diagnostic , COVID-19/virologie , Humains , Facteurs immunologiques/composition chimique , Facteurs immunologiques/isolement et purification , Poumon/vascularisation , Poumon/effets des médicaments et des substances chimiques , Poumon/anatomopathologie , Poumon/virologie , Phaeophyta/composition chimique , Polyosides/composition chimique , Polyosides/isolement et purification , Embolie pulmonaire/complications , Embolie pulmonaire/diagnostic , Embolie pulmonaire/virologie , Insuffisance respiratoire/complications , Insuffisance respiratoire/diagnostic , Insuffisance respiratoire/virologie , Rhodophyta/composition chimique , SARS-CoV-2/effets des médicaments et des substances chimiques , SARS-CoV-2/pathogénicité , Sulfates organiques/composition chimique , Attachement viral/effets des médicaments et des substances chimiques , Pénétration virale/effets des médicaments et des substances chimiques
5.
Bioengineered ; 12(1): 1226-1237, 2021 12.
Article Dans Anglais | MEDLINE | ID: covidwho-1189406

Résumé

The world at large is facing a new threat with the emergence of the Coronavirus Disease 2019 (COVID-19) pandemic. Though imperceptible by the naked eye, the medical, sociological and economical implications caused by this newly discovered virus have been and will continue to be a great impediment to our lives. This health threat has already caused over two million deaths worldwide in the span of a year and its mortality rate is projected to continue rising. In this review, the potential of algae in combating the spread of COVID-19 is investigated since algal compounds have been tested against viruses and algal anti-inflammatory compounds have the potential to treat the severe symptoms of COVID-19. The possible utilization of algae in producing value-added products such as serological test kits, vaccines, and supplements that would either mitigate or hinder the continued health risks caused by the virus is prominent. Many of the characteristics in algae can provide insights on the development of microalgae to fight against SARS-CoV-2 or other viruses and contribute in manufacturing various green and high-value products.


Sujets)
, Microalgues/composition chimique , Extraits de plantes/pharmacologie , Rhodophyta/composition chimique , Animaux , COVID-19/immunologie , COVID-19/prévention et contrôle , COVID-19/virologie , Vaccins contre la COVID-19/génétique , Vaccins contre la COVID-19/immunologie , Humains , Microalgues/génétique , Microalgues/métabolisme , Pandémies , Rhodophyta/génétique , Rhodophyta/métabolisme , SARS-CoV-2/effets des médicaments et des substances chimiques , SARS-CoV-2/génétique , SARS-CoV-2/physiologie
7.
Food Funct ; 11(9): 7415-7420, 2020 Sep 23.
Article Dans Anglais | MEDLINE | ID: covidwho-786676

Résumé

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread around the world at an unprecedented rate. In the present study, 4 marine sulfated polysaccharides were screened for their inhibitory activity against SARS-CoV-2, including sea cucumber sulfated polysaccharide (SCSP), fucoidan from brown algae, iota-carrageenan from red algae, and chondroitin sulfate C from sharks (CS). Of them, SCSP, fucoidan, and carrageenan showed significant antiviral activities at concentrations of 3.90-500 µg mL-1. SCSP exhibited the strongest inhibitory activity with IC50 of 9.10 µg mL-1. Furthermore, a test using pseudotype virus with S glycoprotein confirmed that SCSP could bind to the S glycoprotein to prevent SARS-CoV-2 host cell entry. The three antiviral polysaccharides could be employed to treat and prevent COVID-19.


Sujets)
Antiviraux/pharmacologie , Betacoronavirus/effets des médicaments et des substances chimiques , Phaeophyta/composition chimique , Polyosides/pharmacologie , Rhodophyta/composition chimique , Concombres de mer/composition chimique , Animaux , Antiviraux/composition chimique , Betacoronavirus/physiologie , COVID-19 , Infections à coronavirus/virologie , Humains , Pandémies , Pneumopathie virale/virologie , Polyosides/composition chimique , SARS-CoV-2 , Requins , Sulfates/composition chimique , Pénétration virale/effets des médicaments et des substances chimiques
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