COVID-19 and Cholinergic Anti-inflammatory Pathway: In silico Identification of an Interaction between α7 Nicotinic Acetylcholine Receptor and the Cryptic Epitopes of SARS-CoV and SARS-CoV-2 Spike Glycoproteins
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Abstract
SARS-CoV-2 is the coronavirus that originated in Wuhan in December 2019 and has spread globally. The observation of a low prevalence of smokers among hospitalized COVID-19 patients has led to the development of a hypothesis that nicotine could have protective effects by enhancing the cholinergic anti-inflammatory pathway. Based on clinical data and on modelling and docking experiments we have previously presented the potential interaction between SARS-CoV-2 Spike glycoprotein and nicotinic acetylcholine receptors (nAChRs), due to a “toxin-like” epitope on the Spike Glycoprotein, with homology to a sequence of a snake venom toxin. We here present that this epitope coincides with the well-described cryptic epitope for the human antibody CR3022 and with the epitope for the recently described COVA1-16 antibody. Both antibodies are recognizing neighboring epitopes, are not interfering with the ACE2 protein and are not able to inhibit SARS-CoV and SARS-CoV-2 infections. In this study we present the molecular complexes of both SARS-CoV and SARS-CoV-2 Spike Glycoproteins, at their open or closed conformations, with the molecular model of the human α7 nAChR. We found that the interface of all studied protein complexes involves a large part of the “toxin-like” sequences of SARS-CoV and SARS-CoV-2 Spike glycoproteins and toxin binding site of human α7 nAChR.
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SciScore for 10.1101/2020.08.20.259747: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Antibodies Sentences Resources Structure retrieval: The 3D structures of the SARS-CoV-2 Spike glycoprotein (S1) in complex with the human Angiotensin Converting Enzyme 2 (hACE2) (PDB id: 6LZG), the hACE2 (1R41, 1R42) the cryo-EM determined complex of spike protein S-ACE2-B0AT1 neutral amino acid transporter (PDB id: 6M18), the structure of a neutralizing to SARS-CoV mAb that also cross-reacts with the S protein of SARS-CoV-2 when the latter is in complex with the ACE2 receptor (PDB id: 6NB7), the ECD of the nAChR α9 subunit in complex with α-bungarotoxin (PDB id: 4UY2), the structure of SARS-CoV-2 RBD in complex with the human … SciScore for 10.1101/2020.08.20.259747: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Antibodies Sentences Resources Structure retrieval: The 3D structures of the SARS-CoV-2 Spike glycoprotein (S1) in complex with the human Angiotensin Converting Enzyme 2 (hACE2) (PDB id: 6LZG), the hACE2 (1R41, 1R42) the cryo-EM determined complex of spike protein S-ACE2-B0AT1 neutral amino acid transporter (PDB id: 6M18), the structure of a neutralizing to SARS-CoV mAb that also cross-reacts with the S protein of SARS-CoV-2 when the latter is in complex with the ACE2 receptor (PDB id: 6NB7), the ECD of the nAChR α9 subunit in complex with α-bungarotoxin (PDB id: 4UY2), the structure of SARS-CoV-2 RBD in complex with the human monoclonal antibody CR3022 (PDB id:6W41) and the structure of the ligand binding domain (LBD) of a chimera pentameric α7 nAChR (PDB id: 3SQ9) were downloaded from the Protein Data Bank (PDB). 2.3. Angiotensin Converting Enzyme 2suggested: Noneneutral amino acid transportersuggested: Noneα-bungarotoxinsuggested: (Thermo Fisher Scientific Cat# B35451, RRID:AB_2617152)Software and Algorithms Sentences Resources BLAST searches were performed using Mega BLAST [26] with the UNIPROT protein database [27] and by using BLASTP (protein–protein BLAST) with default parameters. BLASTsuggested: (BLASTX, RRID:SCR_001653)Mega BLASTsuggested: (Mega BLAST, RRID:SCR_011920)BLASTPsuggested: (BLASTP, RRID:SCR_001010)Multiple sequence alignments were performed using ClustalOmega program (Clustal-O) [28]. 2.2. ClustalOmegasuggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- No funding statement was detected.
- No protocol registration statement was detected.
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