Inhibitory effects of fucoidan from Laminaria japonica against some pathogenic bacteria and SARS-CoV-2 depend on its large molecular weight.

Fucoidan is a highly sulfated polysaccharide with a wide range of bioactivities, including anti-pathogenic activity. However, the relationship between structure and activity of fucoidan in inhibiting pathogen infections remains unclear. Here, different-molecular-weight fucoidans were prepared by photocatalytic degradation followed by membrane ultrafiltration, and their chemical structures and anti-pathogenic microbiota activity were compared. Results showed that photocatalytic degradation could effectively degrade fucoidan while its structure block and sulfate groups were not destroyed obviously. Fucoidan (90.8 kDa) of 5 mg/mL could inhibit the growth of S. aureus, S. typhimurium and E. coli, but its degradation products, Dfuc1 (19.2 kDa) and Dfuc2 (5.5 kDa), demonstrated lower inhibitory effect. In addition, compared to Dfuc1 and Dfuc2, fucoidan showed stronger capability to prevent the adhesion of S. aureus, L. monocytogenes, V. parahaemolyticus and S. typhimurium to HT-29 cells. Moreover, the inhibitory effect against SARS-CoV-2 and the binding activity to S protein were also positively correlated to molecular weight. These results indicate that natural fucoidan with higher molecular weight are more effective to inhibit these pathogenic bacteria and SARS-CoV-2, providing a better understanding of the relationship between structure and activity of fucoidan against pathogenic microbiota.

Therapeutic Applications of Fucoidans and their Potential to Act against COVID-19.

In this review article, we present the updated evidence of therapeutic applications of fucoidan (a seaweed polysaccharide) and its novel potential to treat infectious diseases such as coronavirus disease (COVID-19). Because of their many biological activities, seaweeds have been identified as a rich and useful source of bioactive chemicals. Sulfated polysaccharides from the sea are considered a source of physiologically active chemicals that might be used in medication development. Antitumor, antiviral, antioxidant, antibacterial, anticoagulant, and immune-inflammatory properties have all been described for these compounds. By interfering at various phases of viral infection, marine sulfated polysaccharide has a virucidal effect. As a result, it opens the door to the development of antiviral treatments. Virus entry into host cells is an initial process, avoiding this type of entry makes any precautionary measure effective. The inhibitory action of certain marine sulfated polysaccharides against coronavirus was tested, and fucoidan, iota-carrageenan, and sea cucumber sulfated polysaccharides all showed a substantial antiviral impact. Fucoidan is one of the useful sulfated polysaccharides that has been widely studied and explored in various research. There are different sources of fucoidans, which have been used in the treatment of viral infection. Additionally, we highlight the mechanism of action of fuocidan against COVID-19. Hence, we could suggest that COVID-19 might be prevented and treated using these sulfated polysaccharides. This review thus highlights ample evidence to support the hypothesis that a large number of drugs have been developed from powerful compounds isolated from marine seaweeds.

Structural characterization and SARS-CoV-2 inhibitory activity of a sulfated polysaccharide from Caulerpa lentillifera.

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.

Seaweed Sulfated Polysaccharides against Respiratory Viral Infections.

Respiratory viral infections have been a leading cause of morbidity and mortality worldwide. Despite massive advancements in the virology field, no specific treatment exists for most respiratory viral infections. Approved therapies against respiratory viruses rely almost exclusively on synthetic drugs that have potential side effects, restricting their use. This review aims to present natural marine sulfated polysaccharides possessing promising antiviral activity against respiratory viruses that could be a safe alternative to synthetic broad-spectrum antiviral drugs. The antiviral properties of marine sulfated polysaccharides are presented according to their mechanism of action on different types and strains of respiratory viruses, and the potential limits of their use are discussed.

Marine sulfated polysaccharides as potential antiviral drug candidates to treat Corona Virus disease (COVID-19).

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.

Heparin: A simplistic repurposing to prevent SARS-CoV-2 transmission in light of its in-vitro nanomolar efficacy.

The world is currently facing a novel coronavirus (SARS-CoV-2) pandemic. The greatest threat that is disrupting the normal functioning of society is the exceptionally high species independent transmission. Drug repurposing is understood to be the best strategy to immediately deploy well-characterized agents against new pathogens. Several repurposable drugs are already in evaluation for determining suitability to treat COVID-19. One such promising compound includes heparin, which is widely used in reducing thrombotic events associated with COVID-19 induced pathology. As part of identifying target-specific antiviral compounds among FDA and world-approved libraries using high-throughput virtual screening (HTVS), we previously evaluated top hits for anti-SARS-CoV-2 activity. Here, we report results of highly efficacious viral entry blocking properties of heparin (IC50 = 12.3 nM) in the complete virus assay, and further, propose ways to use it as a potential transmission blocker. Exploring further, our in-silico analysis indicated that the heparin interacts with post-translational glycoconjugates present on spike proteins. The patterns of accessible spike-glycoconjugates in open and closed states are completely contrasted by one another. Heparin-binding to the open conformation of spike structurally supports the state and may aid ACE2 binding as reported with cell surface-bound heparan sulfate. We also studied spike protein mutant variants' heparin interactions for possible resistance. Based on available data and optimal absorption properties by the skin, heparin could potentially be used to block SARS-CoV-2 transmission. Studies should be designed to exploit its nanomolar antiviral activity to formulate heparin as topical or inhalation-based formulations, particularly on exposed areas and sites of primary viremia e.g. ACE2 rich epithelia of the eye (conjunctiva/lids), nasal cavity, and mouth.