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1.
Cell Mol Biol Lett ; 27(1): 10, 2022 Feb 02.
Article in English | MEDLINE | ID: covidwho-1753103

ABSTRACT

The novel coronavirus disease 2019 (COVID-19) pandemic has spread worldwide, and finding a safe therapeutic strategy and effective vaccine is critical to overcoming severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, elucidation of pathogenesis mechanisms, especially entry routes of SARS-CoV-2 may help propose antiviral drugs and novel vaccines. Several receptors have been demonstrated for the interaction of spike (S) protein of SARS-CoV-2 with host cells, including angiotensin-converting enzyme (ACE2), ephrin ligands and Eph receptors, neuropilin 1 (NRP-1), P2X7, and CD147. The expression of these entry receptors in the central nervous system (CNS) may make the CNS prone to SARS-CoV-2 invasion, leading to neurodegenerative diseases. The present review provides potential pathological mechanisms of SARS-CoV-2 infection in the CNS, including entry receptors and cytokines involved in neuroinflammatory conditions. Moreover, it explains several neurodegenerative disorders associated with COVID-19. Finally, we suggest inflammasome and JaK inhibitors as potential therapeutic strategies for neurodegenerative diseases.


Subject(s)
COVID-19/drug therapy , Central Nervous System/drug effects , Inflammasomes/drug effects , Neurodegenerative Diseases/drug therapy , Receptors, Virus/genetics , SARS-CoV-2/drug effects , Virus Internalization/drug effects , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Antiviral Agents/therapeutic use , Basigin/genetics , Basigin/metabolism , COVID-19/genetics , COVID-19/metabolism , COVID-19/virology , Central Nervous System/metabolism , Central Nervous System/virology , Ephrins/genetics , Ephrins/metabolism , Gene Expression Regulation , Host-Pathogen Interactions/drug effects , Host-Pathogen Interactions/genetics , Humans , Immunologic Factors/therapeutic use , Inflammasomes/genetics , Inflammasomes/metabolism , Janus Kinase Inhibitors/therapeutic use , Janus Kinases/antagonists & inhibitors , Janus Kinases/genetics , Janus Kinases/metabolism , Neurodegenerative Diseases/genetics , Neurodegenerative Diseases/metabolism , Neurodegenerative Diseases/virology , Neuropilin-1/genetics , Neuropilin-1/metabolism , Receptors, Purinergic P2X7/genetics , Receptors, Purinergic P2X7/metabolism , Receptors, Virus/antagonists & inhibitors , Receptors, Virus/metabolism , SARS-CoV-2/genetics , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Signal Transduction
2.
Int J Neuropsychopharmacol ; 25(1): 1-12, 2022 01 12.
Article in English | MEDLINE | ID: covidwho-1467332

ABSTRACT

From the earliest days of the coronavirus disease 2019 (COVID-19) pandemic, there have been reports of significant neurological and psychological symptoms following Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. This narrative review is designed to examine the potential psychoneuroendocrine pathogenic mechanisms by which SARS-CoV-2 elicits psychiatric sequelae as well as to posit potential pharmacologic strategies to address and reverse these pathologies. Following a brief overview of neurological and psychological sequelae from previous viral pandemics, we address mechanisms by which SARS-CoV-2 could enter or otherwise elicit changes in the CNS. We then examine the hypothesis that COVID-19-induced psychiatric disorders result from challenges to the neuroendocrine system, in particular the hypothalamic-pituitary-adrenal stress axis and monoamine synthesis, physiological mechanisms that are only further enhanced by the pandemic-induced social environment of fear, isolation, and socioeconomic pressure. Finally, we evaluate several FDA-approved therapeutics in the context of COVID-19-induced psychoneuroendocrine disorders.


Subject(s)
COVID-19/virology , Central Nervous System Viral Diseases/virology , Central Nervous System/virology , Neurosecretory Systems/virology , SARS-CoV-2/pathogenicity , Anti-Inflammatory Agents/therapeutic use , Antidepressive Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/physiopathology , COVID-19/psychology , Central Nervous System/drug effects , Central Nervous System/metabolism , Central Nervous System/physiopathology , Central Nervous System Viral Diseases/drug therapy , Central Nervous System Viral Diseases/physiopathology , Central Nervous System Viral Diseases/psychology , Host-Pathogen Interactions , Humans , Neuroimmunomodulation , Neurosecretory Systems/drug effects , Neurosecretory Systems/metabolism , Neurosecretory Systems/physiopathology , Prognosis , Risk Factors , Virus Internalization
3.
Int J Mol Sci ; 22(8)2021 Apr 15.
Article in English | MEDLINE | ID: covidwho-1186972

ABSTRACT

COVID-19 is a severe respiratory disease caused by the newly identified human coronavirus (HCoV) Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The virus was discovered in December 2019, and in March 2020, the disease was declared a global pandemic by the World Health Organization (WHO) due to a high number of cases. Although SARS-CoV-2 primarily affects the respiratory system, several studies have reported neurological complications in COVID-19 patients. Headache, dizziness, loss of taste and smell, encephalitis, encephalopathy, and cerebrovascular diseases are the most common neurological complications that are associated with COVID-19. In addition, seizures, neuromuscular junctions' disorders, and Guillain-Barré syndrome were reported as complications of COVID-19, as well as neurodegenerative and demyelinating disorders. However, the management of these conditions remains a challenge. In this review, we discuss the prevalence, pathogenesis, and mechanisms of these neurological sequelae that are secondary to SARS-CoV-2 infection. We aim to update neurologists and healthcare workers on the possible neurological complications associated with COVID-19 and the management of these disease conditions.


Subject(s)
COVID-19/complications , Nervous System Diseases/drug therapy , Nervous System Diseases/etiology , Central Nervous System/drug effects , Central Nervous System/virology , Cerebrovascular Disorders/drug therapy , Cerebrovascular Disorders/etiology , Cerebrovascular Disorders/virology , Humans , Nervous System Diseases/epidemiology , Nervous System Diseases/virology , Prevalence , SARS-CoV-2/metabolism
4.
Sci Rep ; 11(1): 5402, 2021 03 08.
Article in English | MEDLINE | ID: covidwho-1123146

ABSTRACT

Most multiple sclerosis (MS) patients given currently available disease-modifying drugs (DMDs) experience progressive disability. Accordingly, there is a need for new treatments that can limit the generation of new waves T cell autoreactivity that drive disease progression. Notably, immune cells express GABAA-receptors (GABAA-Rs) whose activation has anti-inflammatory effects such that GABA administration can ameliorate disease in models of type 1 diabetes, rheumatoid arthritis, and COVID-19. Here, we show that oral GABA, which cannot cross the blood-brain barrier (BBB), does not affect the course of murine experimental autoimmune encephalomyelitis (EAE). In contrast, oral administration of the BBB-permeable GABAA-R-specific agonist homotaurine ameliorates monophasic EAE, as well as advanced-stage relapsing-remitting EAE (RR-EAE). Homotaurine treatment beginning after the first peak of paralysis reduced the spreading of Th17 and Th1 responses from the priming immunogen to a new myelin T cell epitope within the CNS. Antigen-presenting cells (APC) isolated from homotaurine-treated mice displayed an attenuated ability to promote autoantigen-specific T cell proliferation. The ability of homotaurine treatment to limit epitope spreading within the CNS, along with its safety record, makes it an excellent candidate to help treat MS and other inflammatory disorders of the CNS.


Subject(s)
Central Nervous System/pathology , Multiple Sclerosis/immunology , T-Lymphocytes/immunology , Taurine/analogs & derivatives , Animals , Antigen Presentation/drug effects , Antigen-Presenting Cells/drug effects , Antigen-Presenting Cells/immunology , Cell Proliferation/drug effects , Central Nervous System/drug effects , Central Nervous System/immunology , Disease Models, Animal , Disease Progression , Encephalomyelitis, Autoimmune, Experimental/immunology , Encephalomyelitis, Autoimmune, Experimental/pathology , Female , Mice, Inbred C57BL , Multiple Sclerosis/pathology , Myelin Proteolipid Protein/immunology , Peptide Fragments/immunology , Recurrence , Spleen/pathology , T-Lymphocytes/drug effects , Taurine/pharmacology , gamma-Aminobutyric Acid/pharmacology
5.
Cell Mol Neurobiol ; 42(3): 489-500, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-706891

ABSTRACT

The world faces an exceptional new public health concern caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), subsequently termed the coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO). Although the clinical symptoms mostly have been characterized, the scientific community still doesn´t know how SARS-CoV-2 successfully reaches and spreads throughout the central nervous system (CNS) inducing brain damage. The recent detection of SARS-CoV-2 in the cerebrospinal fluid (CSF) and in frontal lobe sections from postmortem examination has confirmed the presence of the virus in neural tissue. This finding reveals a new direction in the search for a neurotherapeutic strategy in the COVID-19 patients with underlying diseases. Here, we discuss the COVID-19 outbreak in a neuroinvasiveness context and suggest the therapeutic use of high doses of melatonin, which may favorably modulate the immune response and neuroinflammation caused by SARS-CoV-2. However, clinical trials elucidating the efficacy of melatonin in the prevention and clinical management in the COVID-19 patients should be actively encouraged.


Subject(s)
COVID-19/drug therapy , Central Nervous System/virology , Melatonin/therapeutic use , SARS-CoV-2/pathogenicity , Animals , Brain/drug effects , Brain/pathology , Brain/virology , COVID-19/complications , COVID-19/pathology , Central Nervous System/drug effects , Central Nervous System/pathology , Central Nervous System Agents/pharmacology , Central Nervous System Agents/therapeutic use , Central Nervous System Viral Diseases/drug therapy , Central Nervous System Viral Diseases/pathology , Humans , Melatonin/pharmacology , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use
6.
Med Hypotheses ; 144: 110136, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-671591

ABSTRACT

Neurologic symptoms have been reported in some COVID-19 patients. However, little is known on what factors influence the risk of developing these symptoms. While some studies suggest that exposure to pollution is associated with higher rates of SARS-CoV-2 infection, its role is unknown in the development of neurologic symptoms in COVID-19 patients. The response of the central nervous system (CNS) to a SARS-CoV-2 infection may be influenced by its inflammatory state. Interestingly, environmental pollutants such as particulate matter may have neuroinflammatory effects, providing a possible link between exposure to these pollutants and the outcome of SARS-CoV-2 infection in the CNS. This article explores the hypothesis that the neurologic symptoms in COVID-19 may be exacerbated through a neuroinflammatory mechanism that is promoted by environmental pollutant exposure.


Subject(s)
COVID-19/complications , COVID-19/physiopathology , Environmental Pollutants/adverse effects , Nervous System Diseases/complications , Central Nervous System/drug effects , Central Nervous System/virology , Comorbidity , Environmental Exposure/adverse effects , Humans , Inflammation , Models, Theoretical , Nervous System Diseases/etiology , Particulate Matter , Risk , Treatment Outcome
8.
J Med Virol ; 92(7): 786-790, 2020 07.
Article in English | MEDLINE | ID: covidwho-102134

ABSTRACT

An outbreak of a novel coronavirus (SARS-CoV-2) infection has recently emerged and rapidly spreading in humans causing a significant threat to international health and the economy. Rapid assessment and warning are crucial for an outbreak analysis in response to serious public health. SARS-CoV-2 shares highly homological sequences with SARS-CoVs causing highly lethal pneumonia with respiratory distress and clinical symptoms similar to those reported for SARS-CoV and MERS-CoV infections. Notably, some COVID-19 patients also expressed neurologic signs like nausea, headache, and vomiting. Several studies have reported that coronaviruses are not only causing respiratory illness but also invade the central nervous system through a synapse-connected route. SARS-CoV infections are reported in both patients and experimental animals' brains. Interestingly, some COVID-19 patients have shown the presence of SARS-CoV-2 virus in their cerebrospinal fluid. Considering the similarities between SARS-CoV and SARS-CoV-2 in various aspects, it remains to clarify whether the potent invasion of SARS-CoV-2 may affect in COVID-19 patients. All these indicate that more detailed criteria are needed for the treatment and the prevention of SARS-CoV-2 infected patients. In the absence of potential interventions for COVID-19, there is an urgent need for an alternative strategy to control the spread of this disease.


Subject(s)
Betacoronavirus/pathogenicity , Central Nervous System/virology , Coronavirus Infections/epidemiology , Pandemics , Pneumonia, Viral/epidemiology , Severe Acute Respiratory Syndrome/epidemiology , Antiviral Agents/therapeutic use , Betacoronavirus/genetics , COVID-19 , COVID-19 Testing , Central Nervous System/drug effects , Central Nervous System/pathology , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Coronavirus Infections/prevention & control , Coronavirus Infections/virology , Headache/diagnosis , Headache/physiopathology , Headache/virology , Humans , Lung/drug effects , Lung/pathology , Lung/virology , Middle East Respiratory Syndrome Coronavirus/genetics , Middle East Respiratory Syndrome Coronavirus/pathogenicity , Nausea/diagnosis , Nausea/physiopathology , Nausea/virology , Pandemics/prevention & control , Pneumonia, Viral/diagnosis , Pneumonia, Viral/prevention & control , Pneumonia, Viral/virology , Public Health/methods , SARS Virus/genetics , SARS Virus/pathogenicity , SARS-CoV-2 , Severe Acute Respiratory Syndrome/diagnosis , Severe Acute Respiratory Syndrome/prevention & control , Severe Acute Respiratory Syndrome/virology , Viral Vaccines/biosynthesis , Viral Vaccines/therapeutic use , Vomiting/diagnosis , Vomiting/physiopathology , Vomiting/virology
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