Debulking different Corona (SARS-CoV-2 delta, omicron, OC43) and Influenza (H1N1, H3N2) virus strains by plant viral trap proteins in chewing gums to decrease infection and transmission

Henry Daniell, Smruti K. Nair, Hancheng Guan, Yuwei Guo, Rachel J. Kulchar, Marcelo D.T. Torres, Md Shahed-Al-Mahmud, Geetanjali Wakade, Yo Min Liu, Andrew D. Marques, Jevon Graham-Wooten, Wan Zhou, Ping Wang, Sudheer K. Molugu, William R. de Araujo, Cesar de la Fuente-Nunez, Che Ma, William R. Short, Pablo Tebas, Kenneth B. MarguliesFrederic D. Bushman, Francis K. Mante, Robert P. Ricciardi, Ronald G. Collman, Mark S. Wolff

Research output: Contribution to journalArticlepeer-review

Abstract

Because oral transmission of SARS-CoV-2 is 3–5 orders of magnitude higher than nasal transmission, we investigated debulking of oral viruses using viral trap proteins (CTB-ACE2, FRIL) expressed in plant cells, delivered through the chewing gum. In omicron nasopharyngeal (NP) samples, the microbubble count (based on N-antigen) was significantly reduced by 20 μg of FRIL (p < 0.0001) and 0.925 μg of CTB-ACE2 (p = 0.0001). Among 20 delta or omicron NP samples, 17 had virus load reduced below the detection level of spike protein in the RAPID assay, after incubation with the CTB-ACE2 gum powder. A dose-dependent 50% plaque reduction with 50–100 ng FRIL or 600–800 μg FRIL gum against Influenza strains H1N1, H3N2, and Coronavirus HCoV-OC43 was observed with both purified FRIL, lablab bean powder or gum. In electron micrographs, large/densely packed clumps of overlapping influenza particles and FRIL protein were observed. Chewing simulator studies revealed that CTB-ACE2 release was time/dose-dependent and release was linear up to 20 min chewing. Phase I/II placebo-controlled, double-blinded clinical trial (IND 154897) is in progress to evaluate viral load in saliva before or after chewing CTB-ACE2/placebo gum. Collectively, this study advances the concept of chewing gum to deliver proteins to debulk oral viruses and decrease infection/transmission.

Original languageEnglish (US)
Article number121671
JournalBiomaterials
Volume288
DOIs
StatePublished - Sep 2022

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Fingerprint

Dive into the research topics of 'Debulking different Corona (SARS-CoV-2 delta, omicron, OC43) and Influenza (H1N1, H3N2) virus strains by plant viral trap proteins in chewing gums to decrease infection and transmission'. Together they form a unique fingerprint.

Cite this