Prior to the pandemic, Daniell had been studying the angiotensin-converting enzyme 2 (ACE2) protein in the context of treating high blood pressure. By bombarding plant product with the DNA of target proteins, they coax plant chloroplasts to take up the DNA and start growing the proteins. The receptor for ACE2 on human cells also occurs to bind the SARS-CoV-2 spike protein. Penn Dental Medicines Henry Daniell and coworkers used a plant-based protein drug production platform to grow the ACE2 protein, which was then instilled in chewing gum. By either obstructing the ACE2 receptor or binding to the SARS-CoV-2 spike protein, the ACE2 in the gum appears to be able to lower viral entry into cells.
” SARS-CoV-2 replicates in the salivary glands, and we understand that when someone who is infected sneezes, coughs, or speaks a few of that virus can be expelled and reach others,” says Daniell. “This gum provides an opportunity to neutralize the virus in the saliva, offering us a basic way to potentially reduce a source of disease transmission.”
Vaccinations for COVID-19 have actually helped change the course of the pandemic however havent marked out transmission. Even individuals who are totally immunized can still end up being infected with SARS-CoV-2 and, according to current research study, can bring a viral load similar to those who are unvaccinated.
In a procedure of viral load utilizing microbubbles, the chewing gum infused with the ACE2 protein activated a decrease in the amount of infection in samples drawn from COVID-19 patients. Credit: Courtesy of the researchers
Prior to the pandemic, Daniell had been studying the angiotensin-converting enzyme 2 (ACE2) protein in the context of dealing with high blood pressure. His lab had actually grown this protein, along with lots of others that might have healing potential, using a patented plant-based production system. By bombarding plant material with the DNA of target proteins, they coax plant chloroplasts to use up the DNA and begin growing the proteins. The plant material, ground-up and freeze-dried, might be used as a means of delivering the protein. This system has the prospective to avoid the typical obstacles to protein drug synthesis: specifically, an expensive production and filtration procedure.
Daniells past work on ACE2 showed fortuitous in the context of the COVID-19 pandemic. The receptor for ACE2 on human cells likewise takes place to bind the SARS-CoV-2 spike protein. Other research groups have revealed that injections of ACE2 can minimize viral load in people with extreme infections.
Another line of work by Daniell and Penn Dental Medicine coworker Hyun (Michel) Koo has involved research study to establish a chewing gum instilled with plant-grown proteins to interrupt dental plaque. Pairing his insights about ACE2 with this technology, Daniell wondered if such a gum, instilled with plant-grown ACE2 proteins, could neutralize SARS-CoV-2 in the mouth.
To discover, he reached out to Ronald Collman at Penn Medicine, a virologist and lung and crucial care medical professional whose group, considering that the early phases of the pandemic, had actually been gathering blood, nasal swabs, saliva, and other biospecimens from COVID patients for clinical research study.
Penn Dental Medicines Henry Daniell and coworkers used a plant-based protein drug production platform to grow the ACE2 protein, which was then instilled in chewing gum. By either blocking the ACE2 receptor or binding to the SARS-CoV-2 spike protein, the ACE2 in the gum seems able to lower viral entry into cells. Credit: Courtesy of the scientists
” Henry contacted me and asked if we had samples to check his technique, what type of samples would be suitable to test, and whether we might internally confirm the level of SARS-CoV-2 infection in the saliva samples,” Collman says. “That led to a cross-school cooperation structure on our microbiome studies.”
To test the chewing gum, the group grew ACE2 in plants, matched with another substance that allows the protein to cross mucosal barriers and facilitates binding, and incorporated the resulting plant product into cinnamon-flavored gum tablets. Breeding samples acquired from nasopharyngeal swabs from COVID-positive clients with the gum, they revealed that the ACE2 present might neutralize SARS-CoV-2 viruses.
Those initial investigations were followed by others at The Wistar Institute and Penn Vet, in which infections, less-pathogenic than SARS-CoV-2, were modified to reveal the SARS-CoV-2 spike protein. The researchers observed that the gum mostly avoided the viruses or viral particles from going into cells, either by blocking the ACE2 receptor on the cells or by binding directly to the spike protein.
Henry Daniell Credit: Penn Dental Medicine
The team exposed saliva samples from COVID-19 patients to the ACE2 gum and found that levels of viral RNA fell so drastically to be almost undetected.
When checked in people contaminated with SARS-CoV-2, the research study team is currently working towards acquiring approval to perform a clinical trial to assess whether the approach is safe and effective.
” Henrys method of making the proteins in plants and using them orally is low-cost, ideally scalable; it truly is clever,” Collman states.
The research is still in early phases of development, if the medical trials show the gum is safe and effective, it might be offered to clients whose infection status is unidentified or even for a dental check-ups when masks should be gotten rid of, to minimize the likelihood of passing the virus to caregivers.
” We are already utilizing masks and other physical barriers to lower the chance of transmission,” says Daniell. “This gum could be used as an extra tool because fight.”
Recommendation: “Debulking 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, 10 November 2021, Molecular Therapy.DOI: 10.1016/ j.ymthe.2021.11.008.
Henry Daniell is vice chair and the W. D. Miller Professor in the Department of Translational and fundamental 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 Pennsylvanias Perelman School of Medicine.
Daniells coauthors on the paper were Penn Dental Medicines Smruti K. Nair, Nardana Esmaeili, Geetanjali Wakade, Naila Shahid, Prem Kumar Ganesan, Md Reyazul Islam, Manunya Nuth, and Robert Ricciardi; Penn Medicines Sheng Feng, Selene Nuñez Cruz, Jevon Graham-Wooten, Michael Milone, Ping Wang, Kenneth B. Margulies, and Ronald G. Collman; Penn Vets Ariel Shepley-McTaggart and Ronald N. Harty; The Wistar Institutes Ebony N. Gary, Ali R. Ali, and David B. Weiner; and Fraunhofer USAs Stephen J. Streatfield, Rubén Montoya-López, Paul Kaznica, Margaret Mawson, and Brian J. Green.
The study was supported by the National Institutes of Health (grants HL107904, HL109442, AI070077, hl137063, and hl133191), 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.
A chewing gum laced with a plant-grown protein works as a “trap” for the SARS-CoV-2 virus, minimizing viral load in saliva and possibly tamping down transmission, according to a new research study.
The work, led by Henry Daniell at Penns School of Dental Medicine and carried out in collaboration with researchers at the Perelman School of Medicine and School of Veterinary Medicine, in addition to at The Wistar Institute and Fraunhofer USA, could lead to an affordable tool in the toolbox against the COVID-19 pandemic. Their study was published in the journal Molecular Therapy.