Asialoglycoprotein receptor 1 promotes SARS-CoV-2 infection of human normal hepatocytes

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 14, 2024

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes multi-organ damage, which includes hepatic dysfunction, as observed in over 50% of COVID-19 patients. Angiotensin I converting enzyme (peptidyl-dipeptidase A) (ACE2) is the primary receptor for SARS-CoV-2 entry into host cells, and studies have shown presence intracellular virus particles human hepatocytes that express ACE2, but at extremely low levels. Consequently, we asked if might receptors other than ACE2 capable promoting cells. To address this question, performed a genome-wide CRISPR-Cas9 activation library screening found Asialoglycoprotein 1 (ASGR1) promoted pseudovirus infection HeLa In Huh-7 simultaneous knockout ASGR1 prevented infection. immortalized THLE-2 hepatocyte cell line parenchymal both barely expressed could successfully establish an However, after treatment with antibody or siRNA targeting ASGR1, rate significantly dropped, suggesting infects cells mainly through ASGR1-dependent mechanism. We confirmed interact Spike protein, depends on binding domain (RBD) N-terminal (NTD). Finally, also used Immunohistochemistry electron microscopy to verify infect After inhibiting by siRNA, efficiency live decreased significantly. Collectively, these findings indicate candidate promotes

Language: Английский

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Role of Dipeptidyl Peptidase-4 (DPP4) on COVID-19 Physiopathology

Biomedicines, Journal Year: 2022, Volume and Issue: 10(8), P. 2026 - 2026

Published: Aug. 19, 2022

DPP4/CD26 is a single-pass transmembrane protein with multiple functions on glycemic control, cell migration and proliferation, the immune system, among others. It has recently acquired an especial relevance due to possibility act as receptor or co-receptor for SARS-CoV-2, it been already demonstrated other coronaviruses. In this review, we analyze evidence role of DPP4 COVID-19 risk clinical outcome, its contribution physiopathology. Due pathogenetic links between diabetes mellitus hyperinflammatory response, hallmark cytokine storm developed very often during disease, dive deep into carbohydrate metabolism system regulation. We show that broad spectrum regulated by performed both protease enzyme, well interacting partner molecules surface. addition, provide update inhibitors approved EMA and/or FDA, together newfangled approval generic drugs (in 2021 2022). This review will also cover effects (i.e., gliptins) progression SARS-CoV-2 infection, showing in disturbing disease.

Language: Английский

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The oxygen dissociation curve of blood in COVID-19–An update

Frontiers in Medicine, Journal Year: 2023, Volume and Issue: 10

Published: Feb. 27, 2023

An impressive effect of the infection with SARS-Co-19 is impairment oxygen uptake due to lung injury. The reduced diffusion may potentially be counteracted by an increase in affinity hemoglobin. However, hypoxia and anemia associated COVID-19 usually decrease a rise [2,3-bisphosphoglycerate]. As such, related changes dissociation curve critical for supply, but are hard predict. A Pubmed search lists 14 publications on COVID-19. While some investigations show no changes, three large studies found increased that was good prognosis. Exact causes remain unknown. cause under discussion. Erythrocytes structural alterations membrane cytoskeleton have been observed, virus binding Band 3 also ACE2 receptors erythroblasts has proposed. presentation moderate many subjects suffering from sickle cell disease. possible explanation counteracts unfavorable right shift these patients. Under discussion therapy mainly affinity-increasing drugs.

Language: Английский

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Convergent Evolution Dynamics of SARS-CoV-2 and HIV Surface Envelope Glycoproteins Driven by Host Cell Surface Receptors and Lipid Rafts: Lessons for the Future

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 1923 - 1923

Published: Jan. 18, 2023

Although very different, in terms of their genomic organization, enzymatic proteins, and structural HIV SARS-CoV-2 have an extraordinary evolutionary potential common. Faced with various selection pressures that may be generated by treatments or immune responses, these RNA viruses demonstrate high adaptive capacities, which result the continuous emergence variants quasi-species. In this retrospective analysis viral ensuring adhesion to plasma membrane host cells, we highlight many common points suggest convergent mechanisms evolution. first recognize a lipid raft microdomain acts as landing strip for particles on cell surface. case mucosal are primary targets both viruses, microdomains enriched anionic glycolipids (gangliosides) forming global electronegative field. Both use rafts surf surface search protein receptor able trigger fusion process. This implies envelope proteins geometrically electrically compatible biomolecules they select invade cells. present study, identify electrostatic critical parameter controlling evolution dynamics HIV-1 discuss impact phenotypic properties viruses. The virological data accumulated since early 1980s should help us face future virus pandemics.

Language: Английский

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How Infection and Vaccination Are Linked to Acute and Chronic Urticaria: A Special Focus on COVID-19

Viruses, Journal Year: 2023, Volume and Issue: 15(7), P. 1585 - 1585

Published: July 20, 2023

Since more than a century ago, there has been awareness of the connection between viral infections and onset exacerbation urticaria. Our knowledge about role infection vaccination in acute chronic urticaria improved as result COVID-19 pandemic but it also highlighted gaps. Viral infections, especially respiratory tract like COVID-19, can trigger (AU) (CU). Less frequently, against viruses including SARS-CoV-2 lead to new well worsening CU minority. Here, with particular focus on we review what is known vaccinations triggers causes We discuss possible mechanistic pathways outline unmet needs our knowledge. Although underlying mechanisms are not clearly understood, believed that signals, medications, stress activate skin mast cells (MCs). Further studies needed fully understand relevance better clarify causal pathways.

Language: Английский

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Autoimmunity and Immunodeficiency in Severe SARS-CoV-2 Infection and Prolonged COVID-19

Current Issues in Molecular Biology, Journal Year: 2022, Volume and Issue: 45(1), P. 33 - 50

Published: Dec. 21, 2022

SARS-CoV-2 causes the complex and heterogeneous illness known as COVID-19. The disease primarily affects respiratory system but can quickly become systemic, harming multiple organs leading to long-lasting sequelae in some patients. Most infected individuals are asymptomatic or present mild symptoms. Antibodies, complement, immune cells efficiently eliminate virus. However, 20% of develop severe organ failure. Virus replication has been described several patients who died from COVID-19, suggesting a compromised response. Immunodeficiency autoimmunity responsible for this impairment facilitate viral escape. Mutations IFN signal transduction T cell activation inadequate response young individuals. Autoantibodies accountable secondary immunodeficiency with infection prolonged Antibodies against cytokines (interferons α, γ ω, IL1β, IL6, IL10, IL-17, IL21), chemokines, nuclear proteins DNA, anticardiolipin, extracellular have reported. type titer autoantibodies depend on age gender. Organ-specific Their role is under study. Autoimmunity should be screened risk factors

Language: Английский

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SARS-CoV-2 infection and immune responses

AIMS Microbiology, Journal Year: 2023, Volume and Issue: 9(2), P. 245 - 276

Published: Jan. 1, 2023

<abstract> <p>The recent pandemic caused by the SARS-CoV-2 virus continues to be an enormous global challenge faced healthcare sector. Availability of new vaccines and drugs targeting sequelae COVID-19 has given world hope in ending pandemic. However, emergence mutations viral genome every couple months different parts is a persistent danger public health. Currently there no single treatment eradicate risk COVID-19. The widespread transmission due Omicron variant necessitates continued work on development implementation effective vaccines. Moreover, evidence that receptor domain spike glycoprotein led decrease current vaccine efficacy escaping antibody recognition. Therefore, it essential actively identify mechanisms which evades host immune system, study long-lasting effects develop therapeutics infections humans preclinical models. In this review, we describe pathogenic infection as well innate adaptive responses infection. We address ongoing need provide protection against variants SARS-CoV-2, validated endpoint assays evaluate immunogenicity pipeline, medications, anti-viral drug therapies health measures, will required successfully end pandemic.</p> </abstract>

Language: Английский

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Morphology and Function of Red Blood Cells in COVID-19 Patients: Current Overview 2023

Life, Journal Year: 2024, Volume and Issue: 14(4), P. 460 - 460

Published: April 1, 2024

In severe cases, SARS-CoV-2 infection leads to respiratory failure. Although angiotensin-converting enzyme 2 (ACE2) receptors are not expressed in red blood cells, can interact with cells (RBCs) via several or auxiliary membrane proteins. Recent data show that viral causes significant damage the RBCs, altering their morphology, deformability, and aggregability. Loss of RBC deformability and/or increased aggregability favors development thrombotic processes microcirculation, as has been described occur COVID-19 patients. addition, many patients also develop systemic endotheliitis associated generalized coagulopathy. This manifests itself clinically obstructive microthrombi area medium smallest vessels, which affect all internal organs. It is thought such changes RBCs may contribute microangiopathy/microthrombosis result impaired capillary flow tissue oxygenation.

Language: Английский

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Impaired VEGF-A-Mediated Neurovascular Crosstalk Induced by SARS-CoV-2 Spike Protein: A Potential Hypothesis Explaining Long COVID-19 Symptoms and COVID-19 Vaccine Side Effects?

Microorganisms, Journal Year: 2022, Volume and Issue: 10(12), P. 2452 - 2452

Published: Dec. 12, 2022

Long coronavirus disease-19 (COVID-19) is a newly discovered syndrome characterized by multiple organ manifestations that persist for weeks to months, following the recovery from acute disease. Occasionally, neurological and cardiovascular side effects mimicking long COVID-19 have been reported in recipients of vaccines. Hypothetically, clinical similarity could be due shared pathogenic role severe respiratory coronavirus-2 (SARS-CoV-2) spike (S) protein produced virus or used immunization. The S can bind neuropilin (NRP)-1, which normally functions as coreceptor vascular endothelial growth factor (VEGF)-A. By antagonizing docking VEGF-A NRP-1, disrupt physiological pathways involved angiogenesis nociception. One consequence increase unbound forms other receptors. SARS-CoV-2-infected individuals may exhibit increased plasma levels during both illness convalescence, responsible diffuse microvascular damage. A few studies suggest serum also potential biomarker COVID-19, whereas evidence vaccines lacking merits further investigation.

Language: Английский

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Long COVID in Children: A Multidisciplinary Review

Diagnostics, Journal Year: 2023, Volume and Issue: 13(12), P. 1990 - 1990

Published: June 7, 2023

Long COVID syndrome has emerged as a long-lasting consequence of acute SARS-CoV-2 infection in adults. In addition, children may be affected by COVID, with potential clinical issues different fields, including problems school performance and daily activities. Yet, the pathophysiologic bases are largely unknown, it is difficult to predict who will develop syndrome. this multidisciplinary review, we summarise latest scientific data regarding its impact on children. Special attention given diagnostic tests, order help physicians find disease markers quantify impairment. Specifically, assess respiratory, upper airways, cardiac, neurologic motor psychological aspects. Finally, also propose approach.

Language: Английский

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