Could a Sugar Test Help to Protect Us Against a Future Pandemic?

Peter Russell

January 17, 2022

With world attention still focused on COVID-19, which continues to wreak havoc around the globe, the World Health Organization (WHO) has appealed to scientists to broaden their interest to the potential for a future 'disease X'.

The number of high threat pathogens, such as SARS, MERS, Lassa, Ebola, and avian influenza, have been increasing in recent years.

November saw the inaugural meeting of WHO's Scientific Advisory Group for the Origins of Novel Pathogens (SAGO) established to address "serious gaps in the global capacity to prepare for, prevent, detect, and respond rapidly to outbreaks with epidemic and pandemic potential", in the words of WHO director-general Dr Tedros Adhanom Ghebreyesus.

Glycan Flow-through Spot Testing

In a collaboration between industry and academia, one UK company is developing a novel diagnostic test for monitoring pathogens, including those that could evolve to become the next pandemic.

With a need to develop testing capable of producing faster and more accurate results, Iceni Glycoscience is working on a test to identify viruses, such as animal influenza, that could jump to humans, not by looking for viral nucleic acids or protein targets, but by detecting complex sugar chains.

The prototype test targets these glycans, that coat the surface of all human cells, and are used as a 'handle' to which a virus can attach itself.

"They find the carbohydrates that are on our cell surfaces, and that's how they infect us," the company's glycobiology research and development manager, Dr Michael Rugen PhD, told Medscape UK.

He explained: "Sugar is not just glucose, it's a suite of biomolecules that are very complicated in terms of their chemistry, and they're very, very varied. In nature, you find a lot of variety of different types of carbohydrates, and it's that variety that allows us to then go in and pick at specific ones."

Proof of concept for a next generation glycan-based rapid diagnostic test was a partnership between the University of Warwick, Iceni Glycoscience, and University Hospitals Coventry and Warwickshire NHS Trust.

The resulting study, published in October last year in the journal  ACS Sensors , demonstrated that a glyco-lateral flow-through device, similar in size to the lateral flow test (LFT) widely used during the current pandemic, could be developed for detecting viruses, either as an alternative, or to complement antibody-based LFTs.

The prototype, that targeted the sialic acid-binding site of the spike protein of SARS-CoV-2, achieved 85% sensitivity and 93% specificity, the researchers said. They demonstrated that mutations in the virus do not remove glycan binding, so lateral-flow and flow-through glyco-assays have the potential to detect a range of viruses, they said.

Viral Mutations

According to Dr Rugen, testing for pathogens using antibodies depends on prior knowledge of the virus structure, whereas a glycan-based test would be "more mutation proof", so that, "if a virus mutates significantly, as with the COVID pandemic - we didn't know the sequence of what was causing this until we’d got samples, grown them up and sequenced them - whereas what we can do is test without knowing anything in advance".

The University of Warwick has since licenced its intellectual property to Norwich-based Iceni Glycoscience, a spin-out from the University of East Anglia and the John Innes Centre, to accelerate commercial development.

Current strategy is focused on their use in testing laboratories to assess what type of viral strains bind to different sugars. "I would hope that the general public don't have exposure to these types of viruses, so we would be testing for nothing that is there, hopefully," said Dr Rugen. "But we also need to have the ability to do these tests ready, if the pandemic, or if a pandemic, does come out of the influenza strains."

According to Dr Rugen: "It's worth bearing in mind that flu is still there, and [of] previous pandemics that have occurred in the past hundred or so years, four of them have been flu-based, so it really is an important area to monitor".

One barrier to manufacturing the test for wider, public use would require a shift from a the flow-through device used in development, in which the liquid sample is directly deposited and dried onto the strip, with the viral components absorbing onto the stationary phase, to a lateral flow device as in the COVID-19 LFTs, where the line is pre-printed.

Advanced prototyping was outsourced to Bedford-based manufacturer Mologic, a company experienced in developing lateral flow devices and which has the necessary quality systems to facilitate CE marking and regulatory approval.

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