In a recent bioRxiv* paper, a research group from the Marinomed Biotech biopharmaceutical company in Austria showed that a sulfated polysaccharide iota-carrageenan has the propensity to inhibit cell entry of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by using an in vitro neutralization assay.
With millions of individuals affected by the coronavirus disease (COVID-19) pandemic, caused by SARS-CoV-2, enormous pressure has been put on the global research community to find an effective drug or vaccine. Thus far, these efforts have been elusive, albeit several promising candidates surfaced recently.
Iota-carrageenan is a sulfated polysaccharide found in certain species of red seaweed (Chondrus crispus) with already well-established antiviral activity against respiratory viruses, which was primarily demonstrated in cell cultures and animal models.
In a nutshell, this polymer seems to stick directly to viruses, hampering in turn viral attachment to host cells. Consequently, a nasal spray containing various concentrations of iota-carrageenan has been developed and already registered as a medical device, with rhinoviruses being a prime target.
Available clinical data and post-market surveillance showed that iota-carrageenan is well-tolerated, with a rather low number of reported adverse events. Can this be another ray of hope against COVID-19?
With the use of a specific lentiviral system, Austrian Researchers from the Marinomed Biotech in Korneuburg tested the ability of iota-carrageenan and other sulfated polysaccharides to inhibit viral attachment and subsequent cell entry.
Appraising neutralization efficacy of sulfated polymers
In this study, the researchers have utilized a SARS-CoV-2 spike pseudotyped lentivirus to test the neutralization efficacy of a range of sulfated polymers – iota-carrageenan, kappa-carrageenan, lambda-carrageenan, and fucoidans.
The aforementioned SARS-CoV-2 spike pseudotyped lentivirus was recently developed for the study of spike-mediated cell entry by using luciferase reporter activity. More specifically, the attachment of SARS-CoV-2 to cell receptor by using spike protein can be measured via luciferase reporter activity, directly correlating with the efficiency of transduction.
And since the backbone of this virus is comprised of a non-replicating lentivirus, there is actually no infection risk for the personnel involved in research. Therefore, experiments can be conducted in a much less stringent biosafety level 2 environment.
Iota-carrageenan as the 'most valuable player'
The researchers have shown that iota-carrageenan has the propensity to inhibit the cell entry of SARS-CoV-2 spike pseudotyped lentivirus in a dose-dependent manner. Moreover, even low concentrations of iota-carrageenan were capable of neutralizing viral particles.
When iota-carrageenan was compared to other sulfated polymers from different species, it was clear that iota-carrageenan has superior efficacy. SARS-CoV-2 spike pseudotyped lentivirus particles were efficiently neutralized with a half-maximal inhibitory concentration value of 2.6 microgram/ml of iota-carrageenan.
The researchers also hypothesize that the inhibition observed with kappa-carrageenan and lambda-carrageenan is mainly due to the presence of iota-carrageenan in these products as well. Hence, more research with iota-carrageenan, but also better-refined kappa and lambda polymers, is warranted to allow steadfast conclusions on their individual viral blocking effect.
Closing the gap
Previous laboratory data on iota-carrageenan against various rhinoviruses and coronaviruses demonstrated similar half-maximal inhibitory concentration values and readily translated into clinical effectiveness when a nasal spray successfully reduced the duration and severity of the common cold.
"Therefore, our data suggest that treatment with iota-carrageenan either prophylactically or therapeutically may be similarly effective in humans suffering from COVID-19", emphasize study authors in their bioRxiv paper.
These findings are also relevant concerning the development of a vaccine against SARS-CoV-2 and the development of long-lasting neutralizing antibodies since their protective potential will be pivotal for successfully tackling this pandemic.
And if another novel respiratory virus emerges in the future, iota-carrageenan may serve as an initial, non-specific treatment that will close the gap between the identification of a causative agent and the successful development of specific antivirals or vaccines.
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.