tetano
Editor, Senior Moderator
Biomaterials
. 2022 Jul 18;121671.
doi: 10.1016/j.biomaterials.2022.121671. Online ahead of print.
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[SUP] 1 [/SUP], Smruti K Nair[SUP] 2 [/SUP], Hancheng Guan[SUP] 2 [/SUP], Yuwei Guo[SUP] 2 [/SUP], Rachel J Kulchar[SUP] 2 [/SUP], Marcelo D T Torres[SUP] 3 [/SUP], Md Shahed-Al-Mahmud[SUP] 4 [/SUP], Geetanjali Wakade[SUP] 2 [/SUP], Yo-Min Liu[SUP] 4 [/SUP], Andrew D Marques[SUP] 3 [/SUP], Jevon Graham-Wooten[SUP] 3 [/SUP], Wan Zhou[SUP] 3 [/SUP], Ping Wang[SUP] 3 [/SUP], Sudheer K Molugu[SUP] 3 [/SUP], William R de Araujo[SUP] 5 [/SUP], Cesar de la Fuente-Nunez[SUP] 3 [/SUP], Che Ma[SUP] 4 [/SUP], William R Short[SUP] 3 [/SUP], Pablo Tebas[SUP] 3 [/SUP], Kenneth B Margulies[SUP] 3 [/SUP], Frederic D Bushman[SUP] 3 [/SUP], Francis K Mante[SUP] 2 [/SUP], Robert P Ricciardi[SUP] 2 [/SUP], Ronald G Collman[SUP] 3 [/SUP], Mark S Wolff[SUP] 2 [/SUP]
Affiliations
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
. 2022 Jul 18;121671.
doi: 10.1016/j.biomaterials.2022.121671. Online ahead of print.
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[SUP] 1 [/SUP], Smruti K Nair[SUP] 2 [/SUP], Hancheng Guan[SUP] 2 [/SUP], Yuwei Guo[SUP] 2 [/SUP], Rachel J Kulchar[SUP] 2 [/SUP], Marcelo D T Torres[SUP] 3 [/SUP], Md Shahed-Al-Mahmud[SUP] 4 [/SUP], Geetanjali Wakade[SUP] 2 [/SUP], Yo-Min Liu[SUP] 4 [/SUP], Andrew D Marques[SUP] 3 [/SUP], Jevon Graham-Wooten[SUP] 3 [/SUP], Wan Zhou[SUP] 3 [/SUP], Ping Wang[SUP] 3 [/SUP], Sudheer K Molugu[SUP] 3 [/SUP], William R de Araujo[SUP] 5 [/SUP], Cesar de la Fuente-Nunez[SUP] 3 [/SUP], Che Ma[SUP] 4 [/SUP], William R Short[SUP] 3 [/SUP], Pablo Tebas[SUP] 3 [/SUP], Kenneth B Margulies[SUP] 3 [/SUP], Frederic D Bushman[SUP] 3 [/SUP], Francis K Mante[SUP] 2 [/SUP], Robert P Ricciardi[SUP] 2 [/SUP], Ronald G Collman[SUP] 3 [/SUP], Mark S Wolff[SUP] 2 [/SUP]
Affiliations
- PMID: 35953331
- DOI: 10.1016/j.biomaterials.2022.121671
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