Visual Abstract
Topics: Biology, Biotechnology, COVID-19, Research
To advance a novel concept of debulking virus in the oral cavity, the primary site of viral replication, virus-trapping proteins CTB-ACE2 were expressed in chloroplasts and clinical-grade plant material was developed to meet FDA requirements. Chewing gum (2 g) containing plant cells expressed CTB-ACE2 up to 17.2 mg ACE2/g dry weight (11.7% leaf protein), have physical characteristics and taste/flavor like conventional gums, and no protein was lost during gum compression. CTB-ACE2 gum efficiently (>95%) inhibited entry of lentivirus spike or VSV-spike pseudovirus into Vero/CHO cells when quantified by luciferase or red fluorescence. 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. COVID-19 saliva samples showed low or undetectable ACE2 activity when compared with healthy individuals (2,582 versus 50,126 ΔRFU; 27 versus 225 enzyme units), confirming greater susceptibility of infected patients for viral entry. 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. Chewing gum with virus-trapping proteins offers a generally affordable strategy to protect patients from most oral virus re-infections through debulking or minimizing transmission to others.
Debulking SARS-CoV-2 in saliva using angiotensin-converting enzyme 2 in chewing gum to decrease oral virus transmission and infection, Molecular Therapy: Cell.com
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, Ronald G. Collman
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