Chewing Gum Developed That Could Reduce COVID Transmission – Laced With Protein That “Traps” the SARS-CoV-2 Virus

A chewing gum laced with a vegetable protein serves as a “trap” for the SARS-CoV-2 virus, reducing the viral load in the saliva and potentially suppressing transmission, according to a new study.

The work, led by Henry Daniell at Penn’s School of Dental Medicine and conducted in collaboration with scientists from the Perelman School of Medicine and School of Veterinary Medicine, as well as The Wistar Institute and Fraunhofer USA, could lead to an inexpensive 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 someone who is infected sneezes, coughs, or speaks, some of that virus can be expelled and reach others,” Daniell says. “This chewing gum offers the possibility to neutralize the virus in the saliva, allowing us to reduce a source of disease transmission in a simple way.”

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

As a measure of viral load using microbubbles, the chewing gum infused with the ACE2 protein caused a reduction in the amount of virus in samples taken from COVID-19 patients. Credit: Courtesy of the Researchers

Prior to the pandemic, Daniell had studied the angiotensin-converting enzyme 2 (ACE2) protein in the context of treating hypertension. His lab had grown this protein, as well as many others that may have therapeutic potential, using a patented plant-based production system. By bombarding plant material with the DNA of target proteins, they entice the plant’s chloroplasts to take up the DNA and grow 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 previous work on ACE2 turned out to be coincidental in the context of the COVID-19 pandemic. The receptor for ACE2 on human cells also happens to bind to the SARS-CoV-2 spike protein. Other research groups have shown that injections of ACE2 can reduce the viral load in people with severe infections.

Meanwhile, another work by Daniell and Penn Dental Medicine colleague Hyun (Michel) Koo has researched to develop a chewing gum infused with plant proteins to disrupt dental plaque. Daniell linked his insights about ACE2 to this technology and wondered whether such a chewing gum, infused with vegetable ACE2 proteins, could neutralize SARS-CoV-2 in the oral cavity.

To find out, he reached out to Ronald Collman of Penn Medicine, a virologist and pulmonary and critical care physician whose team has been collecting blood, nasal swabs, saliva and other biospecimens from COVID patients since the early stages of the pandemic. Research.

Henry Daniell and colleagues at Penn Dental Medicine used a plant-based protein drug manufacturing platform to grow the ACE2 protein, which was then administered in chewing gum. By either blocking the ACE2 receptor or binding to the SARS-CoV-2 spike protein, the ACE2 in the gums appears to be able to reduce viral access to cells. Credit: Courtesy of the Researchers

“Henry contacted me and asked if we had samples to test his approach, what kind of samples would be appropriate for testing and if we could internally validate the level of SARS-CoV-2 virus in the saliva samples” , says Colman. “That led to a cross-school collaboration that built on our microbiome studies.”

To test the chewing gum, the team cultured ACE2 in plants, combined with another compound that allows the protein to cross mucosal barriers and facilitate binding, and processed the resulting plant material into cinnamon-flavored chewing gum tablets. By incubating samples obtained from nasopharyngeal swabs from COVID-positive patients with the gums, they showed that the ACE2 present could neutralize SARS-CoV-2 viruses.

Those initial studies 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 SARS-CoV-2 spike protein. The scientists noted that the chewing gum largely prevented the viruses or viral particles from entering the cells, either by blocking the ACE2 receptor on the cells or by binding directly to the spike protein.

Henry Daniell Credit: Penn Dental Medicine

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

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

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

Although the study is still in its early stages of development, if the clinical trials show that the gums are safe and effective, it could be given to patients whose infection status is unknown, or even for dental checkups when masks need to be removed, to the chance to pass the virus on to healthcare providers.

“We’re already using masks and other physical barriers to reduce the chances of transmission,” Daniell says. “This gum could be used as an extra tool in that fight.”

Reference: “Debulking of SARS-CoV-2 in Saliva Using Angiotensin Converting Enzyme 2 in Chewing Gum to Reduce Oral Virus Transmission and Infection” by Henry Daniell, Smruti K. Nair, Nardana Esmaeili, Geetanjali Wakade, Naila Shahid, Prem Kumar Ganesan, Md Reyazul Islam, Ariel Shepley-McTaggart, Sheng Feng, Ebony N. Gary, Ali R. Ali, Manunya Nuth, Selene Nunez Cruz, Jevon Graham-Wooten, Stephen J. Streatfield, Ruben Montoya-Lopez, Paul Kaznica, Margaret Mawson, Brian J. Green, Robert Ricciardi, Michael Milone, Ronald N. Harty, Ping Wang, David B. Weiner, Kenneth B. Margulies, and Ronald G. Collman, Nov. 10, 2021, Molecular Therapy.
DOI: 10.116/j.ymthe.2021.11.008

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

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

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

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.