A field that has been gaining momentum over the last decade, glycobiotechnology, the study of complex carbohydrates which have multifaceted applications in various fields including medicine, is emerging as the front line in changing the biosciences landscape.
Carbohydrates, which are long chains of polysaccharides broken down by the body to produce energy, can be converted into renewable energy, in an effort to reduce our dependence on fossils, as they are the largest source of biomass on the planet. And recently, its therapeutic potential has attracted attention.
For example, the breakdown of carbohydrates, which is accelerated by microbial enzymes, can be used to produce not only biomaterials but also pharmaceutical products. In addition, it can be an interesting method of fighting infectious diseases.
Can glycobiotechnology fight the flu?
One company that wants to find new ways to deal with viral infections is AIS Biotech. Founded just four months ago, the company is a French biotech company based in the Alps. AIS Biotech – where AIS stands for Anti-Infective Sugar – aims to combat influenza, more commonly known as the flu.
Affecting nearly five million people worldwide, according to the World Health Organization (WHO), the influenza virus is a seasonal epidemic characterized by chills, sore throat, runny nose, body aches and fatigue. With more than 500,000 deaths recorded annually, severe cases can be fatal, especially for those with respiratory problems, and are considered high risk.
With a mission to not only treat this disease but to prevent it, AIS Biotech has developed GlycoFlu, leveraging the treatment promise behind glycobiotechnology.
When the influenza virus enters a host cell by binding to specific sites on the surface of the host’s glycoproteins and glycolipid receptors – after which, through a process of cellular endocytosis, the cell engulfs the virus before replicating itself – GlycoFlu is designed to thwart the initial binding process.
The drug candidate was able to mimic the oligosaccharide binding site on the natural host surface of the Influenza virus. As a result, it is able to neutralize viruses and prevent attachment to host cell surface complex sugars that act as receptors for cell infection, explains Aurelie Juhem, CEO of AIS Biotech.
Aurelie believes that curbing infection by saturating pathogen receptors with synthetic oligosaccharides to inhibit the initial infection step – which is the binding of the pathogen to the surface of the host cell – is the way to go.
“Cell surface oligosaccharides are the target of many pathogens,” said Aurelie. “In our case, to develop our strategy to prevent infection, glycobiotechnology is a sustainable way to produce tailor-made carbohydrate bioproducts which are the specific active ingredients of our innovative anti-infectives.”
Glycobiotechnology: on the road to sustainable pharmacy
This young biotech has collaborated with the Center for Plant Macromolecule Research CERMAV-CNRS for the development of GlycoFlu, which also aims to promote the production of environmentally friendly biopharmaceutical products. Since the pharmaceutical industry is responsible for generating tens of thousands of metric tons of chemical waste, bioproducts such as GlycoFlu may be a more sustainable alternative to address this looming problem.
Aurelie stated that he was impressed with the bioproduction process which is very efficient and cost-effective with a lower environmental impact when compared to chemical processes.
“As a biologist, I am always motivated by projects that have the potential to positively impact patients, and biotechnology is one of the most dynamic and innovative sectors. Indeed, in recent years, many scientific and technological advances have come from biotechnology, and in many applications such as energy, health, agriculture and food which are the great challenges facing society,” said Aurelie.
Although GlycoFlu is a nascent technology and is still in the process of being manufactured, carbohydrate-based drugs have been around since the 1940s. Antibiotics such as streptomycin and neomycin have been used to treat various bacterial infections including tuberculosis. The former works by interfering with the function of ribosomes – which are where protein synthesis occurs in cells – in bacterial cells, which is similar to the mechanism of action of neomycin. And besides these antibiotics, chemotherapy drugs like doxorubicin, better known by its brand name Adriamycin, consist of deoxy sugars obtained from certain strains of the Streptomyces bacteria. It stops cancer cell growth by blocking the topo isomerase 2 enzyme, and is used in the treatment of many types of cancer including leukemia, lymphoma, neuroblastoma, sarcoma and Wilms tumor, among others.
However, these anti-infective and anticancer drugs are considered as a treatment against disease and not a preventive measure, unlike GlycoFlu.
Currently in the preclinical stage, GlycoFlu has undergone proof-of-concept studies in influenza models both in vivo – after examining mouse models with infection – and ex vivo – in human airway epithelium. In addition, the company is advancing analytical methods and scale-up manufacturing processes.
Can GlycoFlu AIS Biotech target other infectious diseases?
While AIS Biotech’s efforts to target SARS-CoV-2 have not achieved the desired results, because the sialosides (complex sugars) produced to make GlycoFlu are designed only to mimic those targeted by the influenza virus, the startup has identified another pathogen – which has yet to be disclosed because it is still investigated – which can bind to sugar-based receptors. This means that this technology can become a broader platform for addressing the medical needs of patients affected by infectious diseases, through this new mechanism. Aurelie also pointed out that to specifically target pathogens, for example coronaviruses, they would have to prepare different strains of bacteria capable of producing virus-correlated sialosides.
Currently funded through bank loans, grants and personal investments, Aurelie hopes their first fundraiser, which is scheduled to take place soon, will help achieve the company’s first milestone.
“AIS Biotech’s mission is to contribute to the fight against current and emerging infectious diseases,” said Aurelie. “My hope for the future, as CEO of AIS Biotech, is that GlycoFlu and our next drug candidates will be effective in humans to contribute to the ongoing fight against current and emerging diseases.”