Chewing gum that could reduce SARS-CoV-2 tr


Chewing gum containing vegetable protein acts as a “trap” for the SARS-CoV-2 virus, reducing the viral load in saliva and potentially slowing transmission, according to a new study.

The work, led by Henry Daniell at Penn’s School of Dental Medicine and carried out in collaboration with scientists from the Perelman School of Medicine and the School of Veterinary Medicine, as well as the Wistar Institute and Fraunhofer USA, could lead to a low cost tool. in the arsenal against the COVID-19 pandemic. Their study was published in the journal Molecular therapy.

“SARS-CoV-2 replicates in the salivary glands, and we know that when an infected person sneezes, coughs or speaks, part of this virus can be expelled and reach others,” says Daniell. “This gum provides an opportunity to neutralize the virus in saliva, giving us a simple way to potentially reduce a source of disease transmission.”

COVID-19 vaccines have helped change the course of the pandemic but have not eradicated transmission. Even people who are fully vaccinated can still be infected with SARS-CoV-2 and, according to recent research, can carry a viral load similar to those who are not vaccinated.

Prior to the pandemic, Daniell had studied angiotensin converting enzyme 2 (ACE2) protein as part of the treatment of hypertension. His lab had cultivated this protein, along with many others that may have therapeutic potential, using a patented plant-based production system. By bombarding the plant material with the DNA of the target proteins, they cause the plant chloroplasts to take up the DNA and start growing the proteins. The plant material, freeze-dried and ground, could be used as a means of delivering the protein. This system has the potential to avoid the usual obstacles to protein drug synthesis, namely an expensive production and purification process.

Daniell’s earlier work on ACE2 turned out to be fortuitous in the context of the COVID-19 pandemic. The ACE2 receptor on human cells also binds to the SARS-CoV-2 spike protein. Other research groups have shown that ACE2 injections can lower the viral load in people with serious infections.

Meanwhile, another line of work from Daniell and Penn Dental Medicine colleague Hyun (Michel) Koo involved research to develop vegetable protein-infused chewing gum to disrupt dental plaque. Combining his knowledge of ACE2 with this technology, Daniell wondered if such a gum, infused with plant ACE2 proteins, could neutralize SARS-CoV-2 in the oral cavity.

To find out, he contacted Ronald Collman of Penn Medicine, a virologist and pulmonary and intensive care physician whose team, since the early stages of the pandemic, had collected blood, nasal swabs, saliva and other biological samples from COVID patients for scientific research.

“Henry contacted me and asked if we had samples to test his approach, what type of samples would be appropriate to test, and if we could internally validate the level of SARS-CoV-2 virus in the samples. saliva, ”Collman said. “This led to an interschool collaboration based on our microbiome studies. “

To test chewing gum, the team cultivated ACE2 in plants, together with another compound that allows the protein to cross mucous barriers and facilitates binding, and incorporated the resulting plant material into gum tablets. cinnamon. By incubating samples obtained from nasopharyngeal swabs of COVID-positive patients with gum tissue, they showed that the ACE2 present could neutralize SARS-CoV-2 viruses.

These early investigations were followed by others at the Wistar Institute and Penn Vet, in which viruses, less pathogenic than SARS-CoV-2, were modified to express the spike protein SARS-CoV-2. Scientists observed that the gum largely prevents viruses or viral particles from entering cells, either by blocking the ACE2 receptor on the cells or by directly binding to the spike protein.

Finally, the team exposed saliva samples from COVID-19 patients to ACE2 gum and found that viral RNA levels had dropped so dramatically that they were almost undetectable.

The research team is currently working to obtain approval to conduct a clinical trial to assess whether the approach is safe and effective when tested in people infected with SARS-CoV-2.

“Henry’s approach of making the proteins in plants and using them orally is inexpensive and hopefully scalable; it’s really smart, ”Collman says.

Although research is still in the early stages of development, if clinical trials prove that the gum tissue is safe and effective, it could be given to patients with unknown infection status or even for a dental exam when masks need to be. be removed to reduce the likelihood of transmitting the virus to caregivers.

“We already use masks and other physical barriers to reduce the risk of transmission,” says Daniell. “This eraser could be used as an additional tool in this fight.”

Henry Daniell is Vice President and WD Miller Professor in the Department of Basic and Translational Sciences at the School of Dentistry at the University of Pennsylvania.

Ronald Collman is professor of medicine and microbiology and director of the Penn Center for AIDS Research at the Perelman School of Medicine at the University of Pennsylvania.

Daniell’s article co-authors were Smruti K. Nair of Penn Dental Medicine, Nardana Esmaeili, Geetanjali Wakade, Naila Shahid, Prem Kumar Ganesan, Md Reyazul Islam, Manunya Nuth, and Robert Ricciardi; Sheng Feng of Penn Medicine, Selene Nuñez Cruz, Jevon Graham-Wooten, Michael Milone, Ping Wang, Kenneth B. Margulies, and Ronald G. Collman; Ariel Shepley-McTaggart and Ronald N. Harty of Penn Vet; Ebony N. Gary, Ali R. Ali and David B. Weiner of the Wistar Institute; and Stephen J. Streatfield of Fraunhofer USA, Rubén Montoya-López, Paul Kaznica, Margaret Mawson and Brian J. Green.

Daniell holds a patent in this area. Relevant information on patents and applications is available here.

The study was supported by the National Institutes of Health (grants HL107904, HL109442, HL133191, HL137063 and AI070077), the Commonwealth of Pennsylvania, the University of Pennsylvania School of Veterinary Medicine COVID-19 Pilot Award, a Mercatus Center award, the Penn Center for Precision Medicine, Penn Health-Tech, the Penn Center for Innovation and Precision Dentistry, and the NIH RADx program.

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