Titre :

CGRP inhibits SARS-CoV-2 infection of bronchial epithelial cells, and its pulmonary levels correlate with viral clearance in critical COVID-19 patients

Auteur(s) :

Barbosa Bomfim, Caio César [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Génin, Hugo [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Cottoignies-Callamarte, Andréa [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Gallois-Montbrun, Sarah [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Murigneux, Emilie [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Sams, Anette [Auteur]
University of Copenhagen = Københavns Universitet [UCPH]
Rosenberg, Arielle [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Belouzard, Sandrine [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Dubuisson, Jean [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Kosminder, Olivier [Auteur]
Hôpital Cochin [AP-HP]
Pène, Frédéric [Auteur]
Hôpital Cochin [AP-HP]
Terrier, Benjamin [Auteur]
Hôpital Cochin [AP-HP]
Bomsel, Morgane [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Ganor, Yonatan [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]

Titre de la revue :

Journal of virology

Éditeur :

American Society for Microbiology

Date de publication :

2024-08-20

ISSN :

0022-538X

Mot(s)-clé(s) en anglais :

Calu-3 CGRP COVID-19 SARS-CoV-2 SAX
Calu-3
CGRP
COVID-19
SARS-CoV-2
SAX

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), patients with critical coronavirus disease 2019 (COVID-19) present with life-threatening respiratory distress, pulmonary damage, and cytokine ...
Lire la suite >Upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), patients with critical coronavirus disease 2019 (COVID-19) present with life-threatening respiratory distress, pulmonary damage, and cytokine storm. One unexplored component in COVID-19 is the neuropeptide calcitonin gene-related peptide (CGRP), which is highly abundant in the airways and could converge in multiple aspects of COVID-19-related pulmonary pathophysiology. Whether CGRP affects SARS-CoV-2 infection directly remains elusive. We show that in critical COVID-19 patients, CGRP is increased in both plasma and lungs. Importantly, CGRP pulmonary levels are elevated in early SARS-CoV-2-positive patients and restored to baseline upon subsequent viral clearance in SARS-CoV-2-negative patients. We further show that CGRP and its stable analog SAX directly inhibit infection of bronchial Calu-3 epithelial cells with SARS-CoV-2 Omicron and Alpha variants in a dose-dependent manner. Both pre- and post-infection treatments with CGRP and/or SAX are enough to block SARS-CoV-2 productive infection of Calu-3 cells. CGRP-mediated inhibition occurs via activation of the CGRP receptor and involves down-regulation of both SARS-CoV-2 entry receptors at the surface of Calu-3 cells. Together, we propose that increased pulmonary CGRP mediates beneficial viral clearance in critical COVID-19 patients by directly inhibiting SARS-CoV-2 propagation. Hence, CGRP-based interventions could be harnessed for management of COVID-19. IMPORTANCE The neuropeptide CGRP is highly abundant in the airways. Due to its immunomodulatory, vasodilatory, and anti-viral functions, CGRP could affect multiple aspects of COVID-19-related pulmonary pathophysiology. Yet, the interplay between CGRP and SARS-CoV-2 during COVID-19 remains elusive. Herein, we show that pulmonary levels of CGRP are increased in critical COVID-19 patients, at an early stage of their disease when patients are SARS-CoV-2-positive. Upon subsequent viral clearance, CGRP levels are restored to baseline in SARS-CoV-2-negative patients. We further show that pre- and post-infection treatments with CGRP directly inhibit infection of Calu-3 bronchial epithelial cells with SARS -CoV-2, via activation of the CGRP receptor leading to decreased expression of both SARS-CoV-2 entry receptors. Together, we propose that increased pulmonary CGRP is beneficial in COVID-19, as CGRP-mediated inhibition of SARS-CoV-2 infection could contribute to viral clearance in critical COVID-19 patients. Accordingly, CGRP-based formulations could be useful for COVID-19 management.Lire moins >

Langue :

Anglais

Vulgarisation :

Non

Collections :

• Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017

Source :

Harvested from HAL

Date de dépôt :

2024-10-23T02:19:17Z