According to a new study, scientists have found chewing gum laced with a plant-grown protein serves as a “trap” for the SARS-CoV-2 virus, reducing viral load in saliva and potentially tamping down transmission.
The study
The work, led by Henry Daniell at the University of Pennsylvania’s School of Dental Medicine and performed in collaboration with scientists at the Perelman School of Medicine and School of Veterinary Medicine, as well as at 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.
Official comments
“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 said. “This gum offers an opportunity to neutralise the virus in the saliva, giving us a simple way to possibly cut down on a source of disease transmission.”
The lead up
Prior to the pandemic, Daniell had been studying 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 coax plant chloroplasts to take up the DNA and begin growing the proteins. The plant material, freeze-dried and ground-up, 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.
From ACE2 to Covid-19
Daniell’s past work on ACE2 assisted in the context of the Covid-19 pandemic. The receptor for ACE2 on human cells also binds the SARS-CoV-2 spike protein. Other research groups have shown that injections of ACE2 can reduce viral load in people with severe infections.
The chewing gum
Another line of work by Daniell and Penn Dental Medicine colleague Hyun (Michel) Koo has involved research to develop a chewing gum infused with plant-grown proteins to disrupt dental plaque. Pairing his insights about ACE2 with this technology, Daniell wondered if such a gum, infused with plant-grown ACE2 proteins, could neutralise SARS-CoV-2 in the oral cavity.
To find out, he reached out to Ronald Collman at Penn Medicine, a virologist and pulmonary and critical care doctor whose team, since the early stages of the pandemic, had been collecting blood, nasal swabs, saliva, and other biospecimens from Covid patients for scientific research.
To test the chewing gum, the team grew ACE2 in plants, paired with another compound that enables the protein to cross mucosal barriers and facilitates binding, and incorporated the resulting plant material into cinnamon-flavoured gum tablets. Incubating samples obtained from nasopharyngeal swabs from Covid-positive patients with the gum, they showed that the ACE2 present could neutralise SARS-CoV-2 viruses.
Those initial 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 SARS-CoV-2 spike protein. The scientists observed that the gum largely prevented the viruses or viral particles from entering cells, either by blocking the ACE2 receptor on the cells or by binding directly to the spike protein.
Finally, the team exposed saliva samples from Covid-19 patients to the ACE2 gum and found that levels of viral RNA fell so dramatically to be almost undetectable.
The research team is currently working toward obtaining permission to conduct a clinical trial to evaluate whether the approach is safe and effective when tested in people infected with SARS-CoV-2 .
Outlook
Though the research is still in early stages of development, if the clinical trials prove the gum is safe and effective, it could be given to patients whose infection status is unknown or even for dental check-ups to reduce the likelihood of passing the virus to caregivers.
About the scientists
Henry Daniell is Vice Chair and the W. D. Miller Professor in the Department of Basic and Translational Sciences in 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’s Perelman School of Medicine.
Co-authors
Daniell’s coauthors on the paper were Penn Dental Medicine’s Smruti 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 Margulies, and Ronald Collman; Penn Vet’s Ariel Shepley-McTaggart and Ronald Harty; The Wistar Institute’s Ebony Gary, Ali Ali, and David Weiner; and Fraunhofer USA’s Stephen Streatfield, Rubén Montoya-López, Paul Kaznica, Margaret Mawson, and Brian Green.
In a measure of viral load using microbubbles, the chewing gum infused with the ACE2 protein triggered a reduction in the amount of virus in samples taken from Covid-19 patients.
Penn Dental Medicine’s Henry Daniell and colleagues used a plant-based protein drug production platform to grow the ACE2 protein, which was then infused in chewing gum. By either blocking the ACE2 receptor or binding to the SARS-CoV-2 spike protein, the ACE2 in the gum appears to be able to reduce viral entry into cells.Image credit: Researchers and Penn Dental Medicine
