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1.
Int J Mol Sci ; 23(13)2022 Jul 01.
Article in English | MEDLINE | ID: covidwho-1917524

ABSTRACT

Virus-cell fusion is the key step for viral infection in host cells. Studies on virus binding and fusion with host cells are important for understanding the virus-host interaction and viral pathogenesis for the discovery of antiviral drugs. In this review, we focus on the virus-cell fusions induced by the two major pandemic viruses, including the influenza virus and SARS-CoV-2. We further compare the cell fusions induced by the influenza virus and SARS-CoV-2, especially the pH-dependent fusion of the influenza virus and the fusion of SARS-CoV-2 in the type-II transmembrane serine protease 2 negative (TMPRSS2-) cells with syncytia formation. Finally, we present the development of drugs used against SARA-CoV-2 and the influenza virus through the discovery of anti-fusion drugs and the prevention of pandemic respiratory viruses.


Subject(s)
COVID-19 , Orthomyxoviridae , Cell Fusion , Humans , Orthomyxoviridae/metabolism , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/metabolism , Virus Internalization
2.
Viruses ; 13(10)2021 10 14.
Article in English | MEDLINE | ID: covidwho-1469382

ABSTRACT

Respiratory viruses are known to be the most frequent causative mediators of lung infections in humans, bearing significant impact on the host cell signaling machinery due to their host-dependency for efficient replication. Certain cellular functions are actively induced by respiratory viruses for their own benefit. This includes metabolic pathways such as glycolysis, fatty acid synthesis (FAS) and the tricarboxylic acid (TCA) cycle, among others, which are modified during viral infections. Here, we summarize the current knowledge of metabolic pathway modifications mediated by the acute respiratory viruses respiratory syncytial virus (RSV), rhinovirus (RV), influenza virus (IV), parainfluenza virus (PIV), coronavirus (CoV) and adenovirus (AdV), and highlight potential targets and compounds for therapeutic approaches.


Subject(s)
Citric Acid Cycle/physiology , Energy Metabolism/physiology , Fatty Acids/biosynthesis , Glycolysis/physiology , Respiratory Tract Infections/pathology , Respiratory Tract Infections/virology , Adenoviridae/metabolism , Coronavirus/metabolism , Humans , Orthomyxoviridae/metabolism , Parainfluenza Virus 1, Human/metabolism , Respiratory Syncytial Viruses/metabolism , Rhinovirus/metabolism
3.
Cells ; 10(3)2021 03 02.
Article in English | MEDLINE | ID: covidwho-1125490

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19) that has resulted in the current pandemic. The lack of highly efficacious antiviral drugs that can manage this ongoing global emergency gives urgency to establishing a comprehensive understanding of the molecular pathogenesis of SARS-CoV-2. We characterized the role of the nucleocapsid protein (N) of SARS-CoV-2 in modulating antiviral immunity. Overexpression of SARS-CoV-2 N resulted in the attenuation of retinoic acid inducible gene-I (RIG-I)-like receptor-mediated interferon (IFN) production and IFN-induced gene expression. Similar to the SARS-CoV-1 N protein, SARS-CoV-2 N suppressed the interaction between tripartate motif protein 25 (TRIM25) and RIG-I. Furthermore, SARS-CoV-2 N inhibited polyinosinic: polycytidylic acid [poly(I:C)]-mediated IFN signaling at the level of Tank-binding kinase 1 (TBK1) and interfered with the association between TBK1 and interferon regulatory factor 3 (IRF3), subsequently preventing the nuclear translocation of IRF3. We further found that both type I and III IFN production induced by either the influenza virus lacking the nonstructural protein 1 or the Zika virus were suppressed by the SARS-CoV-2 N protein. Our findings provide insights into the molecular function of the SARS-CoV-2 N protein with respect to counteracting the host antiviral immune response.


Subject(s)
Coronavirus Nucleocapsid Proteins/metabolism , DEAD Box Protein 58/metabolism , Interferons/metabolism , Receptors, Immunologic/metabolism , SARS-CoV-2/metabolism , DEAD Box Protein 58/genetics , Host-Pathogen Interactions/genetics , Humans , Interferon Regulatory Factor-3/genetics , Interferon Regulatory Factor-3/metabolism , Interferon Type I/genetics , Interferon Type I/metabolism , Interferon-gamma/genetics , Interferon-gamma/metabolism , Interferons/genetics , Orthomyxoviridae/genetics , Orthomyxoviridae/metabolism , Phosphoproteins/metabolism , Poly C/pharmacology , Poly I/pharmacology , Promoter Regions, Genetic , /metabolism , Receptors, Immunologic/genetics , SARS-CoV-2/genetics , Signal Transduction/drug effects , Signal Transduction/genetics , Transcription Factors/metabolism , Tripartite Motif Proteins/metabolism , Ubiquitin-Protein Ligases/metabolism , Up-Regulation , Zika Virus/genetics , Zika Virus/metabolism
4.
Arch Virol ; 166(3): 733-753, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1064515

ABSTRACT

The chronic dysfunction of neuronal cells, both central and peripheral, a characteristic of neurological disorders, may be caused by irreversible damage and cell death. In 2016, more than 276 million cases of neurological disorders were reported worldwide. Moreover, neurological disorders are the second leading cause of death. Generally, the etiology of neurological diseases is not fully understood. Recent studies have related the onset of neurological disorders to viral infections, which may cause neurological symptoms or lead to immune responses that trigger these pathological signs. Currently, this relationship is mostly based on epidemiological data on infections and seroprevalence of patients who present with neurological disorders. The number of studies aiming to elucidate the mechanism of action by which viral infections may directly or indirectly contribute to the development of neurological disorders has been increasing over the years but these studies are still scarce. Comprehending the pathogenesis of these diseases and exploring novel theories may favor the development of new strategies for diagnosis and therapy in the future. Therefore, the objective of the present study was to review the main pieces of evidence for the relationship between viral infection and neurological disorders such as Alzheimer's disease, Parkinson's disease, Guillain-Barré syndrome, multiple sclerosis, and epilepsy. Viruses belonging to the families Herpesviridae, Orthomyxoviridae, Flaviviridae, and Retroviridae have been reported to be involved in one or more of these conditions. Also, neurological symptoms and the future impact of infection with SARS-CoV-2, a member of the family Coronaviridae that is responsible for the COVID-19 pandemic that started in late 2019, are reported and discussed.


Subject(s)
COVID-19/pathology , Nervous System Diseases/virology , Viral Tropism/physiology , Alzheimer Disease/virology , COVID-19/virology , Epilepsy/virology , Flaviviridae/metabolism , Guillain-Barre Syndrome/virology , Herpesviridae/metabolism , Humans , Multiple Sclerosis/virology , Nervous System Diseases/pathology , Orthomyxoviridae/metabolism , Parkinson Disease/virology , Retroviridae/metabolism , SARS-CoV-2/metabolism
5.
Cardiovasc Res ; 116(12): 1932-1936, 2020 10 01.
Article in English | MEDLINE | ID: covidwho-1017764

ABSTRACT

Angiotensin-converting enzyme 2 (ACE2) has emerged as a key regulator of the renin-angiotensin system in cardiovascular (CV) disease and plays a pivotal role in infections by coronaviruses and influenza viruses. The present review is primarily focused on the findings to indicate the role of ACE2 in the relationship of coronaviruses and influenza viruses to CV disease. It is postulated that the risk of coronavirus or influenza virus infection is high, at least partly due to high ACE2 expression in populations with a high CV risk. Coronavirus and influenza virus vaccine usage in high CV risk populations could be a potential strategy to prevent both CV disease and coronavirus/influenza virus infections.


Subject(s)
Cardiovascular Diseases/enzymology , Coronavirus Infections/virology , Coronavirus/metabolism , Orthomyxoviridae/metabolism , Peptidyl-Dipeptidase A/metabolism , Angiotensin-Converting Enzyme 2 , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Animals , Cardiovascular Diseases/metabolism , Humans
6.
FEBS J ; 287(17): 3672-3676, 2020 09.
Article in English | MEDLINE | ID: covidwho-960854

ABSTRACT

The novel coronavirus SARS-CoV-2 is the causative agent of the global coronavirus disease 2019 (COVID-19) outbreak. In addition to pneumonia, other COVID-19-associated symptoms have been reported, including loss of smell (anosmia). However, the connection between infection with coronavirus and anosmia remains enigmatic. It has been reported that defects in olfactory cilia lead to anosmia. In this Viewpoint, we summarize transmission electron microscopic studies of cilia in virus-infected cells. In the human nasal epithelium, coronavirus infects the ciliated cells and causes deciliation. Research has shown that viruses such as influenza and Sendai attach to the ciliary membrane. The Sendai virus enters cilia by fusing its viral membrane with the ciliary membrane. A recent study on SARS-CoV-2-human protein-protein interactions revealed that the viral nonstructural protein Nsp13 interacts with the centrosome components, providing a potential molecular link. The mucociliary escalator removes inhaled pathogenic particles and functions as the first line of protection mechanism against viral infection in the human airway. Thus, future investigation into the virus-cilium interface will help further the battle against COVID-19.


Subject(s)
Anosmia/metabolism , COVID-19/metabolism , Centrosome/virology , Cilia/virology , Nasal Mucosa/virology , SARS-CoV-2/pathogenicity , Viral Nonstructural Proteins/metabolism , Anosmia/complications , Anosmia/physiopathology , Anosmia/virology , COVID-19/complications , COVID-19/physiopathology , COVID-19/virology , Centrosome/metabolism , Centrosome/ultrastructure , Cilia/metabolism , Cilia/ultrastructure , Host-Pathogen Interactions/genetics , Humans , Methyltransferases/genetics , Methyltransferases/metabolism , Microtubule-Associated Proteins/genetics , Microtubule-Associated Proteins/metabolism , Nasal Mucosa/metabolism , Nasal Mucosa/ultrastructure , Orthomyxoviridae/metabolism , Orthomyxoviridae/pathogenicity , Protein Binding , RNA Helicases/genetics , RNA Helicases/metabolism , SARS-CoV-2/metabolism , Sendai virus/metabolism , Sendai virus/pathogenicity , Severity of Illness Index , Smell/physiology , Viral Nonstructural Proteins/genetics
7.
Nat Commun ; 11(1): 2688, 2020 05 27.
Article in English | MEDLINE | ID: covidwho-432476

ABSTRACT

Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs) are zoonotic pathogens with high fatality rates and pandemic potential. Vaccine development focuses on the principal target of the neutralizing humoral immune response, the spike (S) glycoprotein. Coronavirus S proteins are extensively glycosylated, encoding around 66-87 N-linked glycosylation sites per trimeric spike. Here, we reveal a specific area of high glycan density on MERS S that results in the formation of oligomannose-type glycan clusters, which were absent on SARS and HKU1 CoVs. We provide a comparison of the global glycan density of coronavirus spikes with other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin, where glycosylation plays a known role in shielding immunogenic epitopes. Overall, our data reveal how organisation of glycosylation across class I viral fusion proteins influence not only individual glycan compositions but also the immunological pressure across the protein surface.


Subject(s)
Glycoproteins/immunology , Middle East Respiratory Syndrome Coronavirus , Polysaccharides , Spike Glycoprotein, Coronavirus/immunology , Viral Fusion Proteins/immunology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Cryoelectron Microscopy , Epitopes/chemistry , Epitopes/immunology , Epitopes/metabolism , Glycoproteins/chemistry , Glycoproteins/ultrastructure , Glycosylation , HEK293 Cells , HIV-1/immunology , HIV-1/metabolism , Humans , Immune Evasion/physiology , Lassa virus/immunology , Lassa virus/metabolism , Middle East Respiratory Syndrome Coronavirus/immunology , Middle East Respiratory Syndrome Coronavirus/metabolism , Orthomyxoviridae/immunology , Orthomyxoviridae/metabolism , Polysaccharides/chemistry , Polysaccharides/immunology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/ultrastructure , Viral Fusion Proteins/chemistry , Viral Fusion Proteins/ultrastructure , Viral Proteins/chemistry , Viral Proteins/immunology , Viral Proteins/ultrastructure
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