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Scientists forget an important component in the hunt for the corona vaccine

Photo: peoplecreations, Freepik

What does the coronavirus have in common with a gin and tonic, blood, DNA and leaves? For those who don’t know, I’ll give you another hint: a glass of cola contains 3 tablespoons of it. Sugars.

On February 5, 2020, a team of scientists from China, America and Australia published the first molecular 3D model of an outer particle of the new coronavirus (Figure 1). Many more models have followed since then. Strikingly almost all models omit the sugar molecules on the surface of the virus. A big flaw, because those incomplete 3D models will form the basis of the corona vaccine. If scientists do not take the sugars into account, they cannot design a good vaccine.

Sugar molecules on the surface form a kind of jungle that covers the virus. The model shown below (Figure 2) is one of the few that does shows this. It was published online recently by Robert Woods of Lectenz Bio in Athens. The dark purple clumps are sugars and form a kind of shield around the virus particle.

Figure 1. An example of a 3D-model of a coronavirus particle. It does not show any sugars (Wrapp et al., 2020).
Figure 2. A 3D-model of a coronavirus particle with sugars (in purple). Published online by Robert Woods of Lectenz Bio in Athens.

Vaccine selection

Using the published 3D models, scientists try to predict which pieces of the virus are recognized by an infected person’s immune system. To train the immune systems of healthy people one of those viral pieces is then administered as a vaccine. Such a viral fraction is not dangerous in itself, but the healthy person’s immune system recognizes it as an invader and creates a memory of it. When that person comes in contact with the real virus later in life, their immune system immediately recognizes and fights off the virus.

“Sugars at virus’ surface cover up its features.”

So, what exactly is the problem if researchers omit the sugars on a virus’ surface? I will illustrate this with an example: suppose you are an immune system. You are instructed to hunt down an intruder, a bandit, who is tattooed from head to toe. The scientists will hand you a wanted poster that depicts one of the tattoos. That is the feature, the mark, you will focus on. But the bandit doesn’t run around naked. Many of his tattoos are covered by his pants, sweater and shoes. That is exactly what the sugars at the viral surface do: they cover up the features. By ignoring the sugars, researchers are focusing on a feature of the virus that may be invisible to the immune system. When scientists also consider the shielding effect of sugars, they can select vaccines much more accurately.

And even if the immune system can “see” the features on the virus, then still the chance exists that the immune system cannot reach the virus particle because of the sugar shield. This also applies for medication: if a medicine cannot manoeuvre through the dense jungle of sugars, it cannot clear the virus.

“Scientists should stop looking at the naked virus and start including its sugar outfit”

Production problems

Sugars can also throw a spanner in the works during the production of vaccines. A vaccine consists of pieces of the virus. Scientists make these pieces in production systems: cells of, for example, people, other animals or bacteria. Each of these production systems has its own unique sugar factory, which gives the coronavirus pieces a different sugar coating than they naturally have. One system produces viruses with few sugars (a bandit wearing only a swimsuit: almost all tattoos are visible), while other systems completely pack the virus (a bandit in a jumpsuit, boots, gloves and a ski mask). In the former case, the immune system may focus on a wrong feature (tattoo), which is hidden by sugars in the real virus. In the second case, the vaccine does not offer any features to train the immune system. As such, it will not prepare sufficiently for the real virus.

Some sugar factories produce the sugar sialic acid which, in large numbers, can suppress the immune system. Since a vaccine must properly activate and train the immune system, a vaccine should not contain this sugar. Therefore, scientists should select a production system that does not produce sialic acid or they should “cut” this sugar from the virus after production.

Of course, there are also countless successful vaccines, designed without taking sugars into account. So, the sugars may not be the Holy Grail that lead the world to the corona vaccine. But if scientists stop looking at the naked virus and also include its sugar outfit in the search, we are more likely to have a working vaccine in hand soon.

Read more about the corona virus


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