SARS-CoV-2 Envelope (E) Protein Binds and Activates TLR2 Pathway: A Novel Molecular Target for COVID-19 Interventions.
Viruses
; 14(5)2022 05 08.
Article
in English
| MEDLINE | ID: covidwho-1862917
ABSTRACT
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.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Toll-Like Receptor 2
/
Coronavirus Envelope Proteins
/
SARS-CoV-2
/
COVID-19
Type of study:
Experimental Studies
Topics:
Vaccines
Limits:
Humans
Language:
English
Year:
2022
Document Type:
Article
Affiliation country:
V14050999
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