University of Pennsylvania-led Study Team Reveal ACE2 Chewing Gum Just Might Inhibit SARS-CoV-2 Oral Transmission

A study led by the University of Pennsylvania, Department of Medicine, and other research institutes such as Wistar Institute sought to advance a chewing gum that could decrease oral transmission and infection associated with COVID-19. A prominent group of esteemed scientists and physicians suggest that chewing gum with virus-tapping proteins could introduce an economical approach to protecting patients from a majority of oral-based viral reinfections via “debulking” or minimizing transmission to others.

TrialSite briefly breaks down this research for all.

What is the issue?

The SARS-CoV-2 virus spreads through droplets and/or aerosol transmission and is most concerning in close quarters where people are close together. Infected individuals more easily spread it to others or “transmit” the pathogen infecting others.

What attempts have been made to inhibit this problem?

Masking and social distancing have been the primary means that public health authorities have sought to reduce the spread of COVID-19. However, some projects in public setting buildings involve the improvement of air exchanges via filtration.

What is the primary way the pathogen is spread?

The most contagious scenario is in closed quarters where people talk, breathe, or cough near someone else. In fact, according to the recent study, most people emit >100 times smaller aerosols (< μm) during these interactions.

What about vaccination?

Well, most of the world isn’t vaccinated, and frankly, it was never reasonable that the World Health Organization and other pandemic preparation and response teams to think that 70%+ of the world could be vaccinated within a year or two—it is just unreasonable and hints of removed elites that don’t understand how the world works.

In fact, vaccine hesitancy continues to be a big problem, especially in cultures where Western medicine isn’t trusted. Moreover, Western governments have made profound mistakes in positioning the vaccine as a cure. It is not—rather, it could be a useful measure, such as an influenza shot on an annual basis.  

But importantly, the influenza shot doesn’t stop all people from becoming infected with the flu, just like the current crop of COVID-19 vaccines don’t work too well after several months. Vaccine effectiveness wanes, and boosters are required. Yet, what are the long-term consequences of this regimen? We do not know yet.

Vaccination is an important strategy to reduce hospitalization and death, but it doesn’t stop viral transmission, especially after several months. 

What is causing viral strain mutation?

There are different causes. First, the coronavirus pathogen itself is known to mutate—that’s a given. But some believe that the lack of universal vaccination creates reservoirs for mutation. Yet, that mutation would happen anyway! Other scientists, such as Geert Vanden Bossche, believe that the act of mass vaccination in the pandemic itself triggers the conditions for further mutation. There are no studies that prove one argument over the other conclusively.

What is the pressing need?

The reality is that a highly contagious virus has caused over 5 million deaths and 200 million or more infections, thus the need for a way to develop measures to slow down the transmission of infection associated with SARS-CoV-2.

Why did the researchers in this study focus on the oral cavity?

Because that is where the primary site of viral replication occurs.

What did the researchers do?

They sought to “advance a novel concept of debulking virus in the oral activity with virus-tapping proteins CTB-ACE2 expressed in chloroplasts to develop clinical-grade plant material to meet FDA requirements.

What is the investigational product?

Chewing gum (2 g) containing plant cells expressed CTB-ACE2 up to 17 mg ACE/g dry weight (11.7% leaf protein). This investigational product has physical characteristics as well as the taste and flavor like standard chewing gum products. The authors report “no protein was lost during gum compression.”

What were the results of this study?

According to the authors, CTB-ACE2 gum efficiency (>95%) inhibited entry of lentivirus spike or VSV spike pseudovirus in Vero/CHO cells when quantified by luciferase or red fluorescence.

Moreover, they report, “Incubation of CTB-ACE2 microparticles reduced SARS-CoV-2 virus count in COVID-19 swab/saliva samples by >95% when evaluated by microbubbles (femtomolar concentration) or qPCR, demonstrating both virus trapping and blocking of cellular entry.”

Additionally, the authors pointed out that when compared with healthy individuals, COVID-19 saliva samples demonstrated “low or undetectable ACE2 activity (2,582 versus 50,126 ΔRFU; 27 versus 225 enzyme units),” verifying “greater susceptibility of infected patients for viral entry.”

Finally, they note “CTB-ACE2 activity was completely inhibited by pre-incubation with SARS-CoV-2 receptor binding domain, offering an explanation for reduced saliva ACE2 activity among COVID-19 patients.”

What is the authors’ key takeaway?

Chewing gum with “virus-tapping proteins” may represent an economical approach to protect patients from most oral virus reinfections via “debulking or minimizing transmission” to other people nearby.

Who funded the study?

∙ Research in the Daniell laboratory is supported by funding from NIH grants R01 HL 107904 , R01 HL 109442 , and R01 HL 133191

∙ Commonwealth of Pennsylvania, Department of Community and Economic Development grant one corresponding author Henry Daniell, W.D. Miller Professor, Vice-Chair, Department of Basic and Translational Services, University of Pennsylvania on “COVID-19 Pennsylvania Discoveries: Responding to SARS-CoV-2 Through Innovation & Commercialization” funded the purchase of freeze dryers, toxicology studies on ACE2 produced at Fraunhofer USA/AeroFarms, and production of the chewing gum.

∙ Grant supported saliva sample collection in the Collman Lab

∙ Research in the Harty laboratory is supported by funding from a University of Pennsylvania School of Veterinary Medicine COVID-19 Pilot Award, a Mercatus Center award, and NIH T32 grant AI070077 to Ariel Shepley-McTaggart.

∙ Pen Center for Precision Medicine, Penn Health-Tech, Penn Center for Innovation and Precision Dentistry, and NIH RADx program funding supported research in the Wang laboratory.

Lead Research/Investigator (Corresponding Author)

Henry Daniel, Ph.D., W.D. Miller Professor, Vice-Chair, Department of Basic and Translational Services, University of Pennsylvania, Dental Medicine