ArticleCellular and molecular life sciences : CMLS2022
Melatonin drugs inhibit SARS-CoV-2 entry into the brain and virus-induced damage of cerebral small vessels.
Article in Cellular and molecular life sciences : CMLS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Exacerbated Hepatic Stress and Systemic Metabolic Disruption Driven by SARS-CoV-2 P.1 Variant in K18-hACE2 Mice.Immunity, inflammation and disease · 2026Article
- The age-dependent neuroglial interaction with peripheral immune cells in coronavirus-induced neuroinflammation with a special emphasis on COVID-19.Biogerontology · 2025Review
- Molecular Links Between Circadian Rhythm Disruption, Melatonin, and Neurodegenerative Diseases: An Updated Review.Molecules (Basel, Switzerland) · 2025Review
- Computational Design and Evaluation of Peptides to Target SARS-CoV-2 Spike-ACE2 Interaction.Molecules (Basel, Switzerland) · 2025Article
- Review of organ damage from COVID and Long COVID: a disease with a spectrum of pathology.Medical review (2021) · 2025Review
- Melatonin: A potential nighttime guardian against Alzheimer's.Molecular psychiatry · 2025Review
- Melatonin: a ferroptosis inhibitor with potential therapeutic efficacy for the post-COVID-19 trajectory of accelerated brain aging and neurodegeneration.Molecular neurodegeneration · 2024Review
- A mid‑pandemic night's dream: Melatonin, from harbinger of anti‑inflammation to mitochondrial savior in acute and long COVID‑19 (Review).International journal of molecular medicine · 2024Review
- Melatonin: Facts, Extrapolations and Clinical Trials.Biomolecules · 2023Review
- The inhibitory and inactivating effects of visible light on SARS-CoV-2: A narrative update.Journal of photochemistry and photobiology · 2023Article
- Antiviral effect of melatonin on Japanese encephalitis virus infection involves inhibition of neuronal apoptosis and neuroinflammation in SH-SY5Y cells.Scientific reports · 2023Article
- Endothelial dysfunction in COVID-19: an overview of evidence, biomarkers, mechanisms and potential therapies.Acta pharmacologica Sinica · 2023Review
- Development of indolealkylamine derivatives as potential multi-target agents for COVID-19 treatment.European journal of medicinal chemistry · 2023Article
- Chronobiological Efficacy of Combined Therapy of Pelargonium Sidoides and Melatonin in Acute and Persistent Cases of COVID-19: A Hypothetical Approach.Advances in experimental medicine and biology · 2023Review
- Role of aging in Blood-Brain Barrier dysfunction and susceptibility to SARS-CoV-2 infection: impacts on neurological symptoms of COVID-19.Fluids and barriers of the CNS · 2022Review
- Mechanisms and clinical evidence to support melatonin's use in severe COVID-19 patients to lower mortality.Life sciences · 2022Review
- Response to Letter to the Editor from Finsterer: "Encephalitis Associated With SARS-CoV-2 Infection in a Child With Chiari Malformation Type I".In vivo (Athens, Greece)Article
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
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.
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