Title :

Melatonin drugs inhibit SARS-CoV-2 entry into the brain and virus-induced damage of cerebral small vessels.

Author(s) :

Cecon, Erika [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Fernandois, Daniela [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Renault, Nicolas [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Ferreira Coelho, Caio Fernando [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Wenzel, Jan [Auteur]
German Center for Cardiovascular Research [DZHK]
Bedart, Corentin [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Izabelle, Charlotte [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Gallet, Sarah [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Le Poder, Sophie [Auteur]
Virologie UMR1161 [VIRO]
Klonjkowski, Bernard [Auteur]
Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail [ANSES]
Virologie UMR1161 [VIRO]
Schwaninger, Markus [Auteur]
German Center for Cardiovascular Research [DZHK]
Prevot, Vincent [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Dam, Julie [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Jockers, Ralf [Auteur]
Institut Cochin [UMR_S567 / UMR 8104]

Journal title :

Cellular and Molecular Life Sciences

Abbreviated title :

Cell Mol Life Sci

Volume number :

79

Pages :

361

Publication date :

2022-06-15

ISSN :

1420-9071

English keyword(s) :

SARS-CoV-2
COVID-19
Melatonin
Drug repurposing
Brain infection
Neuro-vasculature

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

COVID-19 is a complex disease with short- and long-term respiratory, inflammatory and neurological symptoms that are triggered by the infection with SARS-CoV-2. Invasion of the brain by SARS-CoV-2 has been observed in ...
Show more >COVID-19 is a complex disease with short- and long-term respiratory, inflammatory and neurological symptoms that are triggered by the infection with SARS-CoV-2. Invasion of the brain by SARS-CoV-2 has been observed in humans and is postulated to be involved in post-COVID state. Brain infection is particularly pronounced in the K18-hACE2 mouse model of COVID-19. Prevention of brain infection in the acute phase of the disease might thus be of therapeutic relevance to prevent long-lasting symptoms of COVID-19. We previously showed that melatonin or two prescribed structural analogs, agomelatine and ramelteon delay the onset of severe clinical symptoms and improve survival of SARS-CoV-2-infected K18-hACE2 mice. Here, we show that treatment of K18-hACE2 mice with melatonin and two melatonin-derived marketed drugs, agomelatine and ramelteon, prevents SARS-CoV-2 entry in the brain, thereby reducing virus-induced damage of small cerebral vessels, immune cell infiltration and brain inflammation. Molecular modeling analyses complemented by experimental studies in cells showed that SARS-CoV-2 entry in endothelial cells is prevented by melatonin binding to an allosteric-binding site on human angiotensin-converting enzyme 2 (ACE2), thus interfering with ACE2 function as an entry receptor for SARS-CoV-2. Our findings open new perspectives for the repurposing of melatonergic drugs and its clinically used analogs in the prevention of brain infection by SARS-CoV-2 and COVID-19-related long-term neurological symptoms.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
• Lille Neurosciences & Cognition (LilNCog) - U 1172

Submission date :

2024-01-12T01:16:42Z
2024-01-26T13:36:57Z