TY - JOUR
T1 - 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
AU - Daniell, Henry
AU - Nair, Smruti K.
AU - Guan, Hancheng
AU - Guo, Yuwei
AU - Kulchar, Rachel J.
AU - Torres, Marcelo D.T.
AU - Shahed-Al-Mahmud, Md
AU - Wakade, Geetanjali
AU - Liu, Yo Min
AU - Marques, Andrew D.
AU - Graham-Wooten, Jevon
AU - Zhou, Wan
AU - Wang, Ping
AU - Molugu, Sudheer K.
AU - de Araujo, William R.
AU - de la Fuente-Nunez, Cesar
AU - Ma, Che
AU - Short, William R.
AU - Tebas, Pablo
AU - Margulies, Kenneth B.
AU - Bushman, Frederic D.
AU - Mante, Francis K.
AU - Ricciardi, Robert P.
AU - Collman, Ronald G.
AU - Wolff, Mark S.
N1 - Publisher Copyright:
© 2022 The Author(s)
PY - 2022/9
Y1 - 2022/9
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85137166261&partnerID=8YFLogxK
U2 - 10.1016/j.biomaterials.2022.121671
DO - 10.1016/j.biomaterials.2022.121671
M3 - Article
C2 - 35953331
AN - SCOPUS:85137166261
SN - 0142-9612
VL - 288
JO - Biomaterials
JF - Biomaterials
M1 - 121671
ER -