SARS-CoV-2 Envelope (E) Protein Binds and Activates TLR2 Pathway: A Novel Molecular Target for COVID-19 Interventions
This paper presents a molecular characterization of the interaction between the SARS-CoV-2 envelope (E) protein and TLR2. We demonstrated that the E protein, both as a recombinant soluble protein and as a native membrane protein associated with SARS-CoV-2 viral particles, interacts physically with t...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-05-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/14/5/999 |
| _version_ | 1827665898925719552 |
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| author | Rémi Planès Jean-Baptiste Bert Sofiane Tairi Lbachir BenMohamed Elmostafa Bahraoui |
| author_facet | Rémi Planès Jean-Baptiste Bert Sofiane Tairi Lbachir BenMohamed Elmostafa Bahraoui |
| author_sort | Rémi Planès |
| collection | DOAJ |
| description | This paper presents a molecular characterization of the interaction between the SARS-CoV-2 envelope (E) protein and TLR2. We demonstrated that the E protein, both as a recombinant soluble protein and as a native membrane protein associated with SARS-CoV-2 viral particles, interacts physically with the TLR2 receptor in a specific and dose-dependent manner. Furthermore, we showed that the specific interaction with the TLR2 pathway activates the NF-κB transcription factor and stimulates the production of the CXCL8 inflammatory chemokine. In agreement with the importance of NF-κB in the TLR signaling pathway, we showed that the chemical inhibition of this transcription factor leads to significant inhibition of CXCL8 production, while the blockade of the P38 and ERK1/2 MAP kinases only results in partial CXCL8 inhibition. Overall, our findings propose the envelope (E) protein as a novel molecular target for COVID-19 interventions: either (i) by exploring the therapeutic effect of anti-E blocking/neutralizing antibodies in symptomatic COVID-19 patients, or (ii) as a promising non-spike SARS-CoV-2 antigen candidate for inclusion in the development of next-generation prophylactic vaccines against COVID-19 infection and disease. |
| first_indexed | 2024-03-10T01:36:28Z |
| format | Article |
| id | doaj.art-7157b0e8259a43d9ba8c4f4b90bbff87 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T01:36:28Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-7157b0e8259a43d9ba8c4f4b90bbff872023-11-23T13:31:36ZengMDPI AGViruses1999-49152022-05-0114599910.3390/v14050999SARS-CoV-2 Envelope (E) Protein Binds and Activates TLR2 Pathway: A Novel Molecular Target for COVID-19 InterventionsRémi Planès0Jean-Baptiste Bert1Sofiane Tairi2Lbachir BenMohamed3Elmostafa Bahraoui4Institute of Pharmacology and Structural Biology (IPBS), University of Toulouse, CNRS, 31400 Toulouse, FranceInstitut Toulousain des Maladies Infectieuses et Inflammatoires (INFINITY), INSERM, CNRS, Université Paul Sabatier Toulouse III, 31062 Toulouse, FranceInstitut Toulousain des Maladies Infectieuses et Inflammatoires (INFINITY), INSERM, CNRS, Université Paul Sabatier Toulouse III, 31062 Toulouse, FranceLaboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, School of Medicine, University of California Irvine, Irvine, CA 92697, USAInstitut Toulousain des Maladies Infectieuses et Inflammatoires (INFINITY), INSERM, CNRS, Université Paul Sabatier Toulouse III, 31062 Toulouse, FranceThis paper presents a molecular characterization of the interaction between the SARS-CoV-2 envelope (E) protein and TLR2. We demonstrated that the E protein, both as a recombinant soluble protein and as a native membrane protein associated with SARS-CoV-2 viral particles, interacts physically with the TLR2 receptor in a specific and dose-dependent manner. Furthermore, we showed that the specific interaction with the TLR2 pathway activates the NF-κB transcription factor and stimulates the production of the CXCL8 inflammatory chemokine. In agreement with the importance of NF-κB in the TLR signaling pathway, we showed that the chemical inhibition of this transcription factor leads to significant inhibition of CXCL8 production, while the blockade of the P38 and ERK1/2 MAP kinases only results in partial CXCL8 inhibition. Overall, our findings propose the envelope (E) protein as a novel molecular target for COVID-19 interventions: either (i) by exploring the therapeutic effect of anti-E blocking/neutralizing antibodies in symptomatic COVID-19 patients, or (ii) as a promising non-spike SARS-CoV-2 antigen candidate for inclusion in the development of next-generation prophylactic vaccines against COVID-19 infection and disease.https://www.mdpi.com/1999-4915/14/5/999SARS-CoV-2envelop (E) proteinTLR2CXCL8 |
| spellingShingle | Rémi Planès Jean-Baptiste Bert Sofiane Tairi Lbachir BenMohamed Elmostafa Bahraoui SARS-CoV-2 Envelope (E) Protein Binds and Activates TLR2 Pathway: A Novel Molecular Target for COVID-19 Interventions Viruses SARS-CoV-2 envelop (E) protein TLR2 CXCL8 |
| title | SARS-CoV-2 Envelope (E) Protein Binds and Activates TLR2 Pathway: A Novel Molecular Target for COVID-19 Interventions |
| title_full | SARS-CoV-2 Envelope (E) Protein Binds and Activates TLR2 Pathway: A Novel Molecular Target for COVID-19 Interventions |
| title_fullStr | SARS-CoV-2 Envelope (E) Protein Binds and Activates TLR2 Pathway: A Novel Molecular Target for COVID-19 Interventions |
| title_full_unstemmed | SARS-CoV-2 Envelope (E) Protein Binds and Activates TLR2 Pathway: A Novel Molecular Target for COVID-19 Interventions |
| title_short | SARS-CoV-2 Envelope (E) Protein Binds and Activates TLR2 Pathway: A Novel Molecular Target for COVID-19 Interventions |
| title_sort | sars cov 2 envelope e protein binds and activates tlr2 pathway a novel molecular target for covid 19 interventions |
| topic | SARS-CoV-2 envelop (E) protein TLR2 CXCL8 |
| url | https://www.mdpi.com/1999-4915/14/5/999 |
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