Fight COVID-19 with lettuce chewing gum

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An intriguing new study asks if experimental chewing gum could help fight COVID-19. Alexander Nolting / EyeEm / Getty Images
  • Researchers have developed chewing gum from lettuce that can neutralize SARS-CoV-2 in saliva.
  • They found that viral RNA levels in saliva dropped to almost undetectable levels after exposure to chewing gum.
  • They hypothesize that this experimental gum could help reduce transmission.
  • Researchers are now pushing for chewing gum to enter clinical trials.

SARS-CoV-2 is spread through droplets and aerosols produced when a person infected with the virus speaks, breathes or sings. This is called aerosol transmission.

Therefore, reduce SARS-CoV-2 transmission involves masking, physical distancing, and the use of air filters.

The saliva of symptomatic and asymptomatic people with SARS-CoV-2 contains elevated SARS-CoV-2 viral load. This salivary viral load correlated with the severity of COVID-19 symptoms – a higher viral load is associated with more severe symptoms.

The virus mainly replica inside the salivary glands and oral mucous membranes, making it a potentially high-risk route for the transmission of SARS-CoV-2.

This is especially true for the newer variants – the viral load of people with Delta variant is 1260 times higher than those of the previous strains.

However, viral inactivation in the mouth could be a useful strategy to reduce the spread of the virus.

In a recent study, researchers led by Penn Dental Medicine in Philadelphia, PA, created chewing gum from plant-based materials that can lower the SARS-CoV-2 viral load in saliva.

Medical News Today speak with Henry Daniell, Ph.D., Vice President and Professor WD Miller in the Department of Basic and Translational Sciences at Penn Dental Medicine in Philadelphia, PA, lead author of the study:

“SARS-CoV-2 replicates in the salivary glands. Therefore, the reduction of viruses in the oral cavity should decrease the re-infection of [people with a SARS-CoV-2 infection], in addition to the prevention of transmission.

“So,” Dr. Daniell continued, “[Angiotensin-converting enzyme 2 (ACE2)] the chewing gum should give people with COVID-19 time to build their immunity and reduce the severity of the disease, which is dependent on viral load. ”

“The bioencapsulated proteins in chewing gum are stable and fully functional for several years when stored at room temperature, thus making them affordable by eliminating complex manufacturing processes, expensive cold storage, transportation and other costs associated with current vaccines, ”he added.

“This is an interesting article from the point of view of how biomaterials might have potential in oral drug delivery as well as being used as molecular ‘traps’ for pathogens. ” Semih Tareen, Ph.D., senior director and responsible for research on viral vectors at Biotechnology Sana, who was not involved in the study, said MNT.

“The authors believe that such approaches could help with other potential saliva-replicating viruses, such as Epstein-Barr virus, herpes simplex, [human betaherpesvirus 7], cytomegalovirus, hepatitis C and Zika. This will be an interesting area to follow to see if such biomaterials lead to real use cases, ”explained Dr Tareen.

The current study appears in Molecular therapy.

ACE2 is a protein found on the surface of many types of cells. It serves as a gateway for small proteins to enter cells and regulate their function. It is particularly involved in processes related to blood pressure, wound healing and inflammation.

ACE2 is also the receptor that SARS-CoV-2 uses to enter human cells.

Studies show that people with respiratory distress from COVID-19 have low ACE2 activity. There is also some evidence that injection of soluble ACE2 may restore health in people with the disease.

Before the pandemic, Dr Daniell was studying the ACE2 protein as a way to treat hypertension. His lab has developed a method to cultivate this protein using a patented plant-based production system.

The herbal system works by bombarding plant material with ACE2 DNA to induce its growth in plant chloroplasts. After being lyophilized and crushed, it is ready for delivery to patients, bypassing the costly process of synthesizing drugs.

Along with this research, Dr Daniell and his colleagues studied a chewing gum infused with plant proteins that disrupt dental plaque.

Dr Daniell decided to combine his knowledge of ACE2 and chewing gum to create a gum capable of neutralizing SARS-CoV-2 in the oral cavity.

Dr Daniell contacted Ronald Collman, MD, at Penn Medicine, a virologist and pulmonary and intensive care physician whose team had collected saliva and other biological samples from people with COVID-19 throughout the pandemic.

They began a collaboration to determine if the chewing gum infused with ACE2 could neutralize SARS-CoV-2 in saliva samples.

The researchers first cultivated ACE2 in lettuce plants, with a compound that allows ACE2 to cross mucosal barriers and facilitate binding. They then incorporated these proteins into cinnamon gum and incubated them with nasopharyngeal swabs taken from people who tested positive for SARS-CoV-2.

Researchers found that ACE2 in chewing gum could neutralize SARS-CoV-2 in nasopharyngeal swabs.

Next, the researchers modified the pseudoviruses to express the SARS-CoV-2 spike protein, and then incubated them with the ACE2-infused gum.

In this experiment, the gum prevented viruses from entering cells by blocking the ACE2 receptor or directly binding to the spike protein.

Finally, the researchers exposed saliva samples from people infected with SARS-CoV-2 to both the ACE2-infused gum and a placebo gum. While they found some reduction in the levels of viral RNA in saliva after exposure to the placebo gum, the levels of viral RNA in saliva exposed to the ACE2-infused gum dropped until they became almost undetectable.

According to the authors, previous studies have shown that 48 sugar alcohol compounds, including sorbitol, galactitol, and mannitol, bind to viral proteins, especially VP40 protein within Ebola. The presence of these sugars in the placebo gum may have explained some of its antiviral effects.

When asked to explain the mechanisms behind the ACE2-infused gum on SARS-CoV-2, Dr Daniell said:

“ACE2 uses two different mechanisms: the ACE2 enzyme binds directly to the SARS-CoV-2 spike protein and traps the virus in the chewing gum. In addition, ACE2 binds to its own receptor on oral epithelial cells, thereby blocking the entry of any virus that is not trapped in the chewing gum.

Dr Tareen developed this: “The concept revolves around a molecular ‘trap’ where SARS-CoV-2 is ‘trapped’ by two molecules present on the special drug delivered into the gum tissue. The two molecules are CTB (Cholera nontoxin B) and ACE2.

“ACE2 is a well-known receptor for SARS-CoV-2, while CTB is known to bind to GM1, a cellular glycolipid. [a lipid that maintains the stability of cell membranes and facilitates intercellular interactions] that some studies have shown to be a SARS-CoV-2 co-receptor. The concept of using molecular ‘traps’ like this one for SARS-CoV-2 grabbed headlines earlier with the proposal. nasal sprays. “

The authors conclude that the chewing gum infused with ACE2 may help protect those infected with SARS-CoV-2 and also reduce the risk of transmission to others.

Asked about the limitations of the research, Dr Tareen noted that the study only included three patient samples.

He added: “It is [also] I don’t understand why nasopharyngeal swabs were used for a saliva-based model and how chewing gum in the mouth would affect the viral load at a nearby but still different site. The ddPCR [Droplet Digital polymerase chain reaction] The test used 15 patient saliva samples mixed with gum, but did not actually test gum chewing in people with COVID-19. “

He further noted that findings based on viruses modified to resemble SARS-CoV-2 might not translate into the virus.

Dr Daniell and his team are pushing for the gum to enter clinical trials to assess its safety and effectiveness in people with SARS-CoV-2 to address these issues.

“We have completed the additional toxicological studies required by [the Food and Drug Administration (FDA)], and a revised New Drug Investigation (IND) is [preparing to request] emergency use authorization, “said Dr Daniell,” Due to the successful toxicology studies and this is for topical administration and not an internal drug, early approval is expected. “

“This smart lab study takes advantage of how [SARS-CoV-2] attaches to human cells, initiating infection ”, Dr William Schaffner, professor of preventive medicine in the Department of Health Policy at Vanderbilt University Medical Center in Nashville, TN, said MNT.

“These studies should now be tested in people to determine if ACE2 gum will be accepted.”

“For example, how does it taste and does adding ACE2 interfere with the ‘chewiness’ of the gum?” How long will the protection against infection last? Will people who want protection need to actively chew gum for long periods of time? ” he added.

“Of course, the crucial question is whether ACE2 gum can actually prevent infection. This requires testing on people because they breathe through their nose, and it remains to be seen whether protection extends beyond the oral cavity to the upper part of the throat, the nasopharynx, ”he concluded.

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