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A Functional Interaction Between Y674-R685 Region of the SARS-CoV-2 Spike Protein and the Human α7 Nicotinic Receptor.
Chrestia, Juan Facundo; Oliveira, Ana Sofia; Mulholland, Adrian J; Gallagher, Timothy; Bermúdez, Isabel; Bouzat, Cecilia.
Afiliación
  • Chrestia JF; Instituto de Investigaciones Bioquímicas de Bahía Blanca, Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur-Consejo Nacional de Investigaciones Científicas Y Técnicas (CONICET), Camino La Carrindanga Km 7-8000, Bahía Blanca, Argentina.
  • Oliveira AS; Centre for Computational Chemistry, School of Chemistry, University of Bristol, Bristol, BS8 1TS, UK.
  • Mulholland AJ; Centre for Computational Chemistry, School of Chemistry, University of Bristol, Bristol, BS8 1TS, UK.
  • Gallagher T; School of Chemistry, University of Bristol, Bristol, UK.
  • Bermúdez I; Department of Biological and Medical Sciences, Oxford Brookes University, Oxford, OX3 0BP, UK. ibermudez@brookes.ac.uk.
  • Bouzat C; Instituto de Investigaciones Bioquímicas de Bahía Blanca, Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur-Consejo Nacional de Investigaciones Científicas Y Técnicas (CONICET), Camino La Carrindanga Km 7-8000, Bahía Blanca, Argentina. inbouzat@criba.edu.ar.
Mol Neurobiol ; 59(10): 6076-6090, 2022 Oct.
Article en En | MEDLINE | ID: mdl-35859025
The α7 nicotinic acetylcholine receptor (nAChR) is present in neuronal and non-neuronal cells and has anti-inflammatory actions. Molecular dynamics simulations suggested that α7 nAChR interacts with a region of the SARS-CoV-2 spike protein (S), and a potential contribution of nAChRs to COVID-19 pathophysiology has been proposed. We applied whole-cell and single-channel recordings to determine whether a peptide corresponding to the Y674-R685 region of the S protein can directly affect α7 nAChR function. The S fragment exerts a dual effect on α7. It activates α7 nAChRs in the presence of positive allosteric modulators, in line with our previous molecular dynamics simulations showing favourable binding of this accessible region of the S protein to the nAChR agonist binding site. The S fragment also exerts a negative modulation of α7, which is evidenced by a profound concentration-dependent decrease in the durations of openings and activation episodes of potentiated channels and in the amplitude of macroscopic responses elicited by ACh. Our study identifies a potential functional interaction between α7 nAChR and a region of the S protein, thus providing molecular foundations for further exploring the involvement of nAChRs in COVID-19 pathophysiology.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptor Nicotínico de Acetilcolina alfa 7 / Glicoproteína de la Espiga del Coronavirus / COVID-19 Límite: Humans Idioma: En Revista: Mol Neurobiol Asunto de la revista: BIOLOGIA MOLECULAR / NEUROLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Argentina Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptor Nicotínico de Acetilcolina alfa 7 / Glicoproteína de la Espiga del Coronavirus / COVID-19 Límite: Humans Idioma: En Revista: Mol Neurobiol Asunto de la revista: BIOLOGIA MOLECULAR / NEUROLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Argentina Pais de publicación: Estados Unidos