BREAKING! U.S. Study Finds That The Algal Polysaccharide Rhamnan Sulfate From Monostroma Nitidum Can Be An Effective Antiviral For COVID-19

COVID-19 Supplements: A new study by researchers from Rensselaer Polytechnic Institute-New York, USA and the University of Mississippi-USA has found the algal polysaccharide rhamnan sulfate from the green algae monostroma nitidum can be an effective antiviral for COVID-19 that is organic and safe.

 
Please help to sustain this site and also all our research and community initiatives by making a donation. Your help means a lot and helps saves lives directly and indirectly and we desperately also need financial help now.
https://www.thailandmedical.news/p/sponsorship
 
The pathogen responsible for COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), invades its host through the interaction of its spike (S) protein with a host cell receptor, angiotensin-converting enzyme 2 (ACE2). In addition to ACE2, heparan sulfate (HS) on the surface of host cells also plays a significant role as a co-receptor.
 
Previous studies demonstrated that sulfated glycans, such as heparin and fucoidans, (a long chain sulfated polysaccharide found in various species of brown algae) show anti-COVID-19 activities.
 
Rhamnan sulfate (RS), a polysaccharide with a rhamnose backbone from the green seaweed, Monostroma nitidum, was evaluated for binding to the S-protein from SARS-CoV-2 and inhibition of viral infectivity in vitro.
 
Monostroma is a genus of marine green algae (seaweed) in the family Monostromataceae. As the name suggests, algae of this genus are monostromatic (single cell layered). Monostroma kuroshiense, an algae of this genus, is commercially cultivated in East Asia and South America for the edible product "hitoegusa-nori" or "hirohano-hitoegusa nori", popular sushi wraps. Monostroma oligosaccharides with degree of polymerization 6 prepared by agarase digestion from Monostroma nitidum polysaccharides have been shown to be an effective prophylactic agent during in vitro and in vivo tests against Japanese encephalitis viral infection. The sulfated oligosaccharides from Monostroma seem to be promising candidates as antiviral agents.

The structural characteristics of Rhamnan sulfate or RS were investigated by determining its monosaccharide composition and performing two-dimensional nuclear magnetic resonance. RS inhibition of the interaction of heparin, a highly sulfated HS, with the SARS-CoV-2 spike protein (from wild type and different mutant variants) was studied using surface plasmon resonance (SPR). In competitive binding studies, the IC50 of RS against the S-protein receptor binding domain (RBD) binding to immobilized heparin was 1.6 ng/mL, which is much lower than the IC50 for heparin (~750 ng/mL). RS showed stronger inhibition than heparin on the S-protein RBD or pseudoviral particles binding to immobilized heparin.
 
Finally, in an in vitro cell-based assay, RS showed strong antiviral activities against wild type SARS-CoV-2 and the delta variant.
 
The study findings were published in the peer reviewed journal: Marine Drugs.
https://www.mdpi.com/1660-3397/19/ 12/685
 
To date, there are very few treatments for coronavirus 19 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While incubation, mechanical ventilation, and oxygen supplement can all help, they are only treating the symptoms of the disease.
 
Given the rapid mutation displayed by the virus, more drug candidates are always necessary.
 
The COVID-19 Supplements study team from the Rensselaer Polytechnic Institute in New York have been investigating the potential of rhamnan sulfate (RS) as an antiviral agent for a while now.
 
It is already known that the spike protein of SARS-CoV-2 is key to the pathogenicity of the organism. The receptor-binding domain (RBD) in the S1 subunit binds to receptors such as heparan sulfate and angiotensin-converting enzyme 2 (ACE2) to permit viral cell entry.
 
The study team theorize that rhamnan sulfate or RS can bind to the spike protein and inhibit heparan binding.

Please help to sustain this site and also all our research and community initiatives by making a donation. Your help means a lot and helps saves lives directly and indirectly and we desperately also need financial help now.
https://www.thailandmedical.news/p/sponsorship
 
Utilizing an anion exchange Q-column, the study team extracted and purified the RS from 8g of Monostroma nitidum (Mn) powder.
 
Detailed chromatographic analysis showed a fairly well-balanced monosaccharide composition, with rhamnose as the most prominent sugar.
 
The gel permeation chromatography showed a high (290kDA) molecular weight, and the isolated RS contained 59 (w/w) carbohydrates and 31 (w/w) sulfates.
 
Detailed analysis was performed using nuclear resonance magnetic (NMR) spectroscopy. The backbone of the RS consists largely of →3)-α-L-Rhap-(1→, →2)-α-L-Rhap-(1→, and →2, 3)-α-L-Rhap-(1→units. The intense signal in the C2-C5 regions of the spectrum showed that the C4 hydroxyl groups of the RS are largely sulfated. The non-reducing end of RS is also heavily sulfated at C4/C3.
 
The rhamnose units contained with RS are sulfated at both C2 and C4. On the reducing end of the RS, C1 is assigned at 92-94ppm, but a signal at 96-98ppm suggests that some of these are sulfated. Minor signals of →4)-β-D-GlcAp-(1→ and →6)-β-D-Glcp-(1→ were assigned in the anomeric region.
 
The study team used surface plasmon resonance or SPR (typically used for measuring adsorption) which revealed the binding kinetics and affinity of the RBD (both wild-type and variants) with heparin.
 
Sensorgrams fitted to a 1:1 Langmuir model were used to calculate the binding kinetic parameters. Most of the binding kinetics and affinity are similar when examining wild-type and variants.
 
Interestingly, variant RBDs with the N501Y mutation showed higher affinity to heparin, and L425R mutation showed lower.
 
The study team used solution competition dose-response analysis on immobilized heparin and soluble RS to examine the ability of RS to inhibit the binding of the RBD to heparin. Spike protein was mixed with different concentrations of RS or heparin before injection onto the immobilized heparin.
 
The study findings showed that glycan within the solution occupied some binding sites on the spike protein, allowing the signal to be calculated more accurately. The IC50 value of RS was much lower than the positive control of heparin (1.6ng/mL to ~750ng/mL).
 
The study team also used surface competition experiments using SPR to examine the inhibition of RBD heparin-binding by RS.
 
Interestingly when RS and heparin were at the same concentration, RS showed comparable inhibition against RBD variants containing T478K and improved inhibition against variants containing E484Q and L425R as well as E484Q.
 
Importantly when these experiments were repeated to examine the inhibition RS can cause against pseudovirus particles (both wild-type and delta variant), RS showed improved inhibition against the wild-type and comparable inhibition against the delta pseudovirus particles.
 
The study team investigated the ability of RS to inhibit viral cell entry using a pseudovirus neutralization assay, with HEK cells expressing hACE2. The lowest dilution of RS used reduced viral cell entry by over 80% for both wild-type and Delta-variant pseudoviruses.
 
The study findings highlight that RS effectively binds the spike protein, inhibits viral attachment and exteriorization, uncoating, and the transcription and translation processes. It displays a high capacity to bind the spike protein and successfully neutralizes the pseudotyped virus. It can successfully compete with heparin for spike protein recruitment and work well against a range of variants.
 
Although more investigation is needed, RS is an excellent candidate for future antiviral drugs as it is organic, safe and non-toxic.
 
The study team propose multiple new research angles, including structure-activity relationship, bioavailability, the activity of different molecular weights of RS, and toxicity analysis. If RS proves useful, it could be a powerful tool against COVID-19.
 
Please help to sustain this site and also all our research and community initiatives by making a donation. Your help means a lot and helps saves lives directly and indirectly and we desperately also need financial help now.
https://www.thailandmedical.news/p/sponsorship
 
For more on COVID-19 Supplements, COVID-19 Drugs and COVID-19 Herbs, keep on logging to Thailand Medical News.

Read Also: https://www.thailandmedical.news/news/breaking-covid-19-drugs-study-shows-that-fucoidan-extracted-from-seaweed-outperforms-remdesivir-in-inhibiting-sars-cov-2-in-cell-studies