Everyone knows: the coronavirus can easily spread when corona patients cough, sneeze or even talk. But what if we can already cut the virus off in the mouth? It is being worked on in the US.

Scientists have developed a chewing gum that neutralizes the coronavirus in the mouth. “SARS-CoV-2 multiplies in the salivary glands,” explains researcher Henry Daniell. “And we know that when someone who is infected sneezes, coughs or talks, they can expel some of those virus particles, and then those particles can reach others. This chewing gum offers us the opportunity to neutralize the virus already in the saliva and thus may be a very simple way to reduce a source of transmission.”

How does it work?

The chewing gum that Daniell and colleagues have developed contains the enzyme ACE2. The enzyme itself may not be well known, but most of us are probably familiar with the ACE2 receptor. This is located on our cells and allows the ACE2 enzyme to bind to those cells. The fact that this receptor is now fairly well known has, of course, everything to do with the pandemic that we are still in the middle of, which is caused by SARS-CoV-2: a virus that uses the same ACE2 receptor to – with the help of the now also infamous spike protein – to bind to our cells.


You can compare the ACE2 receptor a bit with a keyhole that fits two keys: the ACE2 enzyme and SARS-CoV-2. The moment one of those two keys is in the keyhole, the other no longer fits. It means that when ACE2 enzymes bind to the ACE2 receptors, SARS-CoV-2 cannot. And in that scenario, the virus cannot invade our cells, cannot multiply and is thus doomed to perish without glory.

But the ACE2 enzyme cannot attach itself to the ACE2 receptor alone. The enzyme can also bind to the spike protein of SARS-CoV-2. And if that happens, the virus also no longer fits in the ‘keyhole’ and can therefore no longer enter our cells and is once again doomed.

Two ways

The chewing gum filled with ACE2 enzymes uses both mechanisms to stop the SARS-CoV-2 virus from entering our cells, Daniell explains. “The ACE2 enzymes in the chewing gum bind directly to the spike protein on SARS-CoV-2 and thus ensure that the virus gets trapped in the chewing gum, as it were. In addition, the ACE2 enzymes bind to their own receptor located on the epithelial cells in the mouth and thus block the cell entry for all virus particles that have not yet become trapped in the gum.”


And the approach works – at least in the laboratory. Because when researchers released the chewing gum on SARS-CoV-2-filled nasal samples from corona patients, the ACE2 enzymes in the gum turned out to be able to keep the virus particles out of our cells and thus neutralize them.

Custom Viruses

Another experiment followed, in which harmless viruses were modified to obtain the spike protein of SARS-CoV-2. Normally, these viruses should have little difficulty entering human cells via the ACE2 receptor. But in lab tests, the chewing gum was found to largely stop the viruses — either by occupying the ACE2 receptors or by coupling to the spike proteins — from entering human cells.


The researchers went one step further. This time they collected some saliva from corona patients and exposed it to the chewing gum. The concentration of virus RNA then fell so sharply that it was almost impossible to detect.

Follow-up research

It is hopeful. But more (clinical) research is needed. so Daniell tells Scientias.nl. For example, it is still unclear how long the chewing gum works. “The ACE2 enzymes are released within fifteen minutes of ingesting the chewing gum. But when you need a new chewing gum depends on virus replication. And during the clinical research, we will have to find out how long it takes for the virus that is already in the salivary glands to multiply and repopulate the saliva. We now expect that to take about four hours.” It would mean that corona patients need a new chewing gum every four hours to neutralize the virus particles in the saliva and thus reduce the chance of infecting others.


Incidentally, it is not only people who have tested positive that the chewing gum benefits, Daniell emphasizes. The chewing gum could also be used preventively in places where contamination via saliva is a real possibility. Consider, for example, the dental practice where people lie in the treatment chair for a long time with their mouth open. “We are already using masks and other physical barriers to reduce the chance of transmission. The chewing gum can be an additional tool in that battle.”


To develop the chewing gum, Daniell and colleagues were able to build on previous work on the angiotensin-converting enzyme 2 (ACE2) for short. This enzyme occurs naturally in our body and plays an important role in regulating blood pressure, among other things. After animal studies showed that additional administration of the enzyme could lower high blood pressure, Daniell decided to look for a way to produce the enzyme on a large scale outside the human body. This with the idea of ​​subsequently being able to offer the enzyme to human patients with high blood pressure in clinical research. And in 2020 there was good news; Daniell and colleagues announced that they had succeeded in getting chlorophyll grains in lettuce to produce ACE2. By then freeze-drying and grinding the lettuce leaves, an ACE2-containing powder was created that could be poured into a pill form. The same method has now been used to make the ACE2 chewing gum. “We put the powder obtained by crushing leaves into a cinnamon-flavored chewing gum,” Daniell says. “In this way we ensure that the ACE2 enzymes are released quickly – as soon as people start chewing.”

scale up

If the clinical trials also yield positive results, it will not be difficult to scale up the production of ACE2, Daniell thinks. “We can produce hundreds of millions of chewing gums in three months.” And these can then be distributed – much more easily than, for example, vaccines. “The proteins that are locked up in the chewing gum are stable at room temperature and remain fully functional even if you store them at room temperature for several years. That makes the chewing gum quite affordable, especially compared to vaccines, because we don’t need a complex production process or expensive storage and transport at low temperatures.” That said, the chewing gum doesn’t make the vaccines obsolete, Daniell points out. He sees the chewing gum as an interim solution. “Until the vaccines are available worldwide, the chewing gum can help to reduce virus transmission and the risk of serious illness after infection (which partly depends on the viral load, or the number of virus particles in the body, ed.).”

But even after the pandemic, Daniell sees plenty of opportunities for chewing gum. “We are looking into what other proteins we can use to trap the flu virus in the chewing gum and prevent it from spreading.”