COVID-19 is still raging across the world, but no drugs or vaccines have been proven safe and effective. At the WLF Frontier Lecture on October 30, Professor Raymond Dwek, Founder and Director of Oxford Glycobiology Institute, Commander of the Order of the British Empire (CBE) Recipient, and Chief Virus Scientist of the British Government, believes that in human’s long fight against viruses, a new weapon is being developed and used, which is glycobiology.
Glycobiology was included in the Oxford English Dictionary in 1993, specifically for describing the science studying the role of glycogen in biological processes. While doing research on antibodies, Dwek and Rodney Porter discovered that glycosylation patterns or types associated with molecules can alter with diseases.
One of the important discoveries in glycobiology is that glycosylation is cell-specific and site-specific. Another key finding is that certain glycoforms attached to glucose residues may participate in glycoprotein folding, which is of great significance for viral envelope glycoproteins that require molecular chaperones.
Dwek cited two examples on the scene. One example was related to the AIDS crisis in 1987, when a scientific team was trying to develop HIV vaccines and antiviral drugs. Among them, Dwek and Max Perutz were responsible for the development of antiviral drugs. Although they successfully made the compounds for HIV clinical trials, the drugs were banned due to side effects. Currently, Dwek’s team has found a way to deal with the problem, namely using iminosugars in the human body, which is the first case where the sugar exerts a positive effect.
As early as 1989, Dwek, Baruch Brumberg and Timothy Niblock jointly discovered that iminosugar-based inhibitors of glucosylceramide synthase could prevent the secretion of hepatitis B virus, with continuing effects after drug withdrawal. Then they conducted many chemical projects to modify iminosugars to see if their antiviral activity could be improved. After a period of research, they got some key structures related to iminosugars.
In short, Dwek and his colleagues found that viral envelope glycoprotein folding is an important antiviral target, and should be mutation-proof as an enzyme in the host cell.
Dwek mentioned that the method adopted by Oxford Glycobiology Institute to treat storage disease is based on using iminosugars to inhibit partial synthesis of glycolipids. Therefore, breaking down less damaged enzymes that may be able to cope with general Gaucher disease. He said that Zavesca, an oral drug for Gaucher disease first produced in 2002, had no serious adverse events reported for more than 18 years. It has been widely available in many countries since 2015.
Gaucher disease is a rare genetic metabolic disease, caused by functional defects of the glucocerebrosidase that is involved in the degradation of the glycosphingolipid sphingosine.
Finally, Dwek pointed out that glycobiology has a promising prospect in the future, and future drug discovery will differ greatly from traditional drug discovery. He emphasized that despite that there is no drug that can directly cure the disease, only with continuing discovery and research can we be better equipped to fight various viruses in our lives more effectively.
It is worth mentioning that as early as February this year, Dwek mentioned to the public that they found that the Zavesca that had been available for a long time may be able to contain novel coronavirus.