tetano
Editor, Senior Moderator
J Virol
. 2024 Aug 20:e0012824.
doi: 10.1128/jvi.00128-24. Online ahead of print. CGRP inhibits SARS-CoV-2 infection of bronchial epithelial cells, and its pulmonary levels correlate with viral clearance in critical COVID-19 patients
Caio César Barbosa Bomfim[SUP] 1 2 [/SUP], Hugo Génin[SUP] 1 2 [/SUP], Andréa Cottoignies-Callamarte[SUP] 1 2 [/SUP], Sarah Gallois-Montbrun[SUP] 2 3 [/SUP], Emilie Murigneux[SUP] 2 3 [/SUP], Anette Sams[SUP] 4 5 [/SUP], Arielle R Rosenberg[SUP] 2 6 [/SUP], Sandrine Belouzard[SUP] 7 [/SUP], Jean Dubuisson[SUP] 7 [/SUP], Olivier Kosminder[SUP] 2 8 [/SUP], Frédéric Pène[SUP] 2 9 [/SUP], Benjamin Terrier[SUP] 2 10 [/SUP], Morgane Bomsel[SUP] 1 2 [/SUP], Yonatan Ganor[SUP] 1 2 [/SUP]
Affiliations
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.IMPORTANCEThe 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.
Keywords: CGRP; COVID-19; Calu-3; SARS-CoV-2; SAX.
. 2024 Aug 20:e0012824.
doi: 10.1128/jvi.00128-24. Online ahead of print. CGRP inhibits SARS-CoV-2 infection of bronchial epithelial cells, and its pulmonary levels correlate with viral clearance in critical COVID-19 patients
Caio César Barbosa Bomfim[SUP] 1 2 [/SUP], Hugo Génin[SUP] 1 2 [/SUP], Andréa Cottoignies-Callamarte[SUP] 1 2 [/SUP], Sarah Gallois-Montbrun[SUP] 2 3 [/SUP], Emilie Murigneux[SUP] 2 3 [/SUP], Anette Sams[SUP] 4 5 [/SUP], Arielle R Rosenberg[SUP] 2 6 [/SUP], Sandrine Belouzard[SUP] 7 [/SUP], Jean Dubuisson[SUP] 7 [/SUP], Olivier Kosminder[SUP] 2 8 [/SUP], Frédéric Pène[SUP] 2 9 [/SUP], Benjamin Terrier[SUP] 2 10 [/SUP], Morgane Bomsel[SUP] 1 2 [/SUP], Yonatan Ganor[SUP] 1 2 [/SUP]
Affiliations
- PMID: 39162434
- DOI: 10.1128/jvi.00128-24
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.IMPORTANCEThe 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.
Keywords: CGRP; COVID-19; Calu-3; SARS-CoV-2; SAX.