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1.
Biomol Concepts ; 13(1): 220-229, 2022 Apr 19.
Article in English | MEDLINE | ID: covidwho-1793459

ABSTRACT

The exposure of organisms and cells to unfavorable conditions such as increased temperature, antibiotics, reactive oxygen species, and viruses could lead to protein misfolding and cell death. The increased production of proteins such as heat shock proteins (HSPs) and polyamines has been linked to protein misfolding sequestration, thus maintaining, enhancing, and regulating the cellular system. For example, heat shock protein 40 (Hsp40) works hand in hand with Hsp70 and Hsp90 to successfully assist the newly synthesized proteins in folding properly. On the other hand, polyamines such as putrescine, spermidine, and spermine have been widely studied and reported to keep cells viable under harsh conditions, which are also involved in cell proliferation, differentiation, and growth. Polyamines are found in all living organisms, including humans and viruses. Some organisms have developed a mechanism to hijack mammalian host cell machinery for their benefit like viruses need polyamines for infection. Therefore, the role of HSPs and polyamines in SARS-CoV-2 (COVID-19) viral infection, how these molecules could delay the effectiveness of the current treatment in the market, and how COVID-19 relies on the host molecules for its successful infection are reviewed.


Subject(s)
COVID-19 , Virus Diseases , Animals , Heat-Shock Proteins , Humans , Mammals/metabolism , Polyamines/metabolism , SARS-CoV-2 , Virus Diseases/metabolism
2.
Cell Signal ; 94: 110325, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1767965

ABSTRACT

Efforts to discover antiviral drugs and diagnostic platforms have intensified to an unprecedented level since the outbreak of COVID-19. Nano-sized endosomal vesicles called exosomes have gained considerable attention from researchers due to their role in intracellular communication to regulate the biological activity of target cells through cargo proteins, nucleic acids, and lipids. According to recent studies, exosomes play a vital role in viral diseases including covid-19, with their interaction with the host immune system opening the door to effective antiviral treatments. Utilizing the intrinsic nature of exosomes, it is imperative to elucidate how exosomes exert their effect on the immune system or boost viral infectivity. Exosome biogenesis machinery is hijacked by viruses to initiate replication, spread infection, and evade the immune response. Exosomes, however, also participate in protective mechanisms by triggering the innate immune system. Besides that, exosomes released from the cells can carry a robust amount of information about the diseased state, serving as a potential biomarker for detecting viral diseases. This review describes how exosomes increase virus infectivity, act as immunomodulators, and function as a potential drug delivery carrier and diagnostic biomarker for diseases caused by HIV, Hepatitis, Ebola, and Epstein-Barr viruses. Furthermore, the review analyzes various applications of exosomes within the context of COVID-19, including its management.


Subject(s)
COVID-19 , Exosomes , Virus Diseases , Antiviral Agents/metabolism , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Biomarkers/metabolism , COVID-19/diagnosis , Endosomes/metabolism , Exosomes/metabolism , Humans , Virus Diseases/diagnosis , Virus Diseases/metabolism
3.
Int J Mol Sci ; 23(4)2022 Feb 19.
Article in English | MEDLINE | ID: covidwho-1715402

ABSTRACT

Platelets, which are small anuclear cell fragments, play important roles in thrombosis and hemostasis, but also actively release factors that can both suppress and induce viral infections. Platelet-released factors include sCD40L, microvesicles (MVs), and alpha granules that have the capacity to exert either pro-inflammatory or anti-inflammatory effects depending on the virus. These factors are prime targets for use in extracellular vesicle (EV)-based therapy due to their ability to reduce viral infections and exert anti-inflammatory effects. While there are some studies regarding platelet microvesicle-based (PMV-based) therapy, there is still much to learn about PMVs before such therapy can be used. This review provides the background necessary to understand the roles of platelet-released factors, how these factors might be useful in PMV-based therapy, and a critical discussion of current knowledge of platelets and their role in viral diseases.


Subject(s)
Blood Coagulation Factors/metabolism , Blood Platelets/metabolism , Extracellular Vesicles/metabolism , Virus Diseases/metabolism , Animals , Cell-Derived Microparticles/metabolism , Humans , Platelet Activation/physiology
4.
Cells ; 11(4)2022 02 17.
Article in English | MEDLINE | ID: covidwho-1715130

ABSTRACT

Mitophagy, which is able to selectively clear excess or damaged mitochondria, plays a vital role in the quality control of mitochondria and the maintenance of normal mitochondrial functions in eukaryotic cells. Mitophagy is involved in many physiological and pathological processes, including apoptosis, innate immunity, inflammation, cell differentiation, signal transduction, and metabolism. Viral infections cause physical dysfunction and thus pose a significant threat to public health. An accumulating body of evidence reveals that some viruses hijack mitophagy to enable immune escape and self-replication. In this review, we systematically summarize the pathway of mitophagy initiation and discuss the functions and mechanisms of mitophagy in infection with classical swine fever virus and other specific viruses, with the aim of providing a theoretical basis for the prevention and control of related diseases.


Subject(s)
Mitophagy , Virus Diseases , Animals , Apoptosis , Immunity, Innate , Mitochondria/metabolism , Mitophagy/physiology , Swine , Virus Diseases/metabolism
5.
Cell Metab ; 34(3): 378-395, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1712531

ABSTRACT

Productive T cell responses to infection and cancer rely on coordinated metabolic reprogramming and epigenetic remodeling among the immune cells. In particular, T cell effector and memory differentiation, exhaustion, and senescence/aging are tightly regulated by the metabolism-epigenetics axis. In this review, we summarize recent advances of how metabolic circuits combined with epigenetic changes dictate T cell fate decisions and shape their functional states. We also discuss how the metabolic-epigenetic axis orchestrates T cell exhaustion and explore how physiological factors, such as diet, gut microbiota, and the circadian clock, are integrated in shaping T cell epigenetic modifications and functionality. Furthermore, we summarize key features of the senescent/aged T cells and discuss how to ameliorate vaccination- and COVID-induced T cell dysfunctions by metabolic modulations. An in-depth understanding of the unexplored links between cellular metabolism and epigenetic modifications in various physiological or pathological contexts has the potential to uncover novel therapeutic strategies for fine-tuning T cell immunity.


Subject(s)
COVID-19 , Neoplasms , Virus Diseases , Aged , Aging , CD8-Positive T-Lymphocytes , Cell Differentiation , Epigenesis, Genetic , Humans , Neoplasms/metabolism , Virus Diseases/metabolism
7.
Eur Rev Med Pharmacol Sci ; 26(2): 715-721, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1675570

ABSTRACT

OBJECTIVE: As N-acetylcysteine (NAC) is promising as a re-purposed drug for the adjunctive or supportive treatment of serious COVID-19, this article aimed to describe current evidence. MATERIALS AND METHODS: A search was performed in PubMed/Medline for "NAC", "viral Infection", COVID-19", oxidative stress", "inflammation", retrieving preclinical and clinical studies. RESULTS: NAC is a pleiotropic molecule with a dual antioxidant mechanism; it may neutralize free radicals and acts as a donor of cysteine, restoring the physiological pool of GSH. Serious COVID-19 patients have increased levels of reactive oxygen species (ROS) and free radicals and often present with glutathione depletion, which prompts a cytokine storm. NAC, which acts as a precursor of GSH inside cells, has been currently used in many conditions to restore or protect against GSH depletion and has a wide safety margin. In addition, NAC has anti-inflammatory activity independently of its antioxidant activity. CONCLUSIONS: Clinical and experimental data suggest that NAC may act on the mechanisms leading to the prothrombotic state observed in severe COVID-19.


Subject(s)
Acetylcysteine/therapeutic use , COVID-19/drug therapy , Acetylcysteine/chemistry , Antioxidants/chemistry , COVID-19/metabolism , COVID-19/virology , Glutathione/chemistry , Glutathione/metabolism , Humans , Oxidative Stress , Randomized Controlled Trials as Topic , Reactive Oxygen Species/metabolism , SARS-CoV-2/isolation & purification , Virus Diseases/drug therapy , Virus Diseases/metabolism
8.
J Neuroinflammation ; 19(1): 8, 2022 Jan 06.
Article in English | MEDLINE | ID: covidwho-1613238

ABSTRACT

BACKGROUND: The serine protease inhibitor nafamostat has been proposed as a treatment for COVID-19, by inhibiting TMPRSS2-mediated viral cell entry. Nafamostat has been shown to have other, immunomodulatory effects, which may be beneficial for treatment, however animal models of ssRNA virus infection are lacking. In this study, we examined the potential of the dual TLR7/8 agonist R848 to mimic the host response to an ssRNA virus infection and the associated behavioural response. In addition, we evaluated the anti-inflammatory effects of nafamostat in this model. METHODS: CD-1 mice received an intraperitoneal injection of R848 (200 µg, prepared in DMSO, diluted 1:10 in saline) or diluted DMSO alone, and an intravenous injection of either nafamostat (100 µL, 3 mg/kg in 5% dextrose) or 5% dextrose alone. Sickness behaviour was determined by temperature, food intake, sucrose preference test, open field and forced swim test. Blood and fresh liver, lung and brain were collected 6 h post-challenge to measure markers of peripheral and central inflammation by blood analysis, immunohistochemistry and qPCR. RESULTS: R848 induced a robust inflammatory response, as evidenced by increased expression of TNF, IFN-γ, CXCL1 and CXCL10 in the liver, lung and brain, as well as a sickness behaviour phenotype. Exogenous administration of nafamostat suppressed the hepatic inflammatory response, significantly reducing TNF and IFN-γ expression, but had no effect on lung or brain cytokine production. R848 administration depleted circulating leukocytes, which was restored by nafamostat treatment. CONCLUSIONS: Our data indicate that R848 administration provides a useful model of ssRNA virus infection, which induces inflammation in the periphery and CNS, and virus infection-like illness. In turn, we show that nafamostat has a systemic anti-inflammatory effect in the presence of the TLR7/8 agonist. Therefore, the results indicate that nafamostat has anti-inflammatory actions, beyond its ability to inhibit TMPRSS2, that might potentiate its anti-viral actions in pathologies such as COVID-19.


Subject(s)
Benzamidines , Guanidines , Inflammation/drug therapy , Serine Endopeptidases/metabolism , Serine Proteinase Inhibitors , Toll-Like Receptor 7/immunology , Virus Diseases/drug therapy , Animals , Benzamidines/pharmacology , Benzamidines/therapeutic use , COVID-19/complications , COVID-19/drug therapy , Guanidines/pharmacology , Guanidines/therapeutic use , Illness Behavior/drug effects , Imidazoles/administration & dosage , Imidazoles/immunology , Inflammation/metabolism , Inflammation/virology , Male , Mice , Serine Proteinase Inhibitors/pharmacology , Serine Proteinase Inhibitors/therapeutic use , Toll-Like Receptor 7/agonists , Virus Diseases/metabolism , Virus Diseases/virology
9.
J Exp Med ; 219(2)2022 02 07.
Article in English | MEDLINE | ID: covidwho-1593236

ABSTRACT

Emerging viruses threaten global health, but few experimental models can characterize the virus and host factors necessary for within- and cross-species transmission. Here, we leverage a model whereby pet store mice or rats-which harbor natural rodent pathogens-are cohoused with laboratory mice. This "dirty" mouse model offers a platform for studying acute transmission of viruses between and within hosts via natural mechanisms. We identified numerous viruses and other microbial species that transmit to cohoused mice, including prospective new members of the Coronaviridae, Astroviridae, Picornaviridae, and Narnaviridae families, and uncovered pathogen interactions that promote or prevent virus transmission. We also evaluated transmission dynamics of murine astroviruses during transmission and spread within a new host. Finally, by cohousing our laboratory mice with the bedding of pet store rats, we identified cross-species transmission of a rat astrovirus. Overall, this model system allows for the analysis of transmission of natural rodent viruses and is a platform to further characterize barriers to zoonosis.


Subject(s)
Disease Models, Animal , Disease Susceptibility , Virus Diseases/etiology , Virus Diseases/transmission , Animal Diseases/transmission , Animal Diseases/virology , Animals , Biomarkers , Host-Pathogen Interactions , Humans , Interferons/metabolism , Mice , Mice, Knockout , Microbial Interactions , Rodentia , Virus Diseases/metabolism
10.
Viruses ; 13(12)2021 11 27.
Article in English | MEDLINE | ID: covidwho-1574265

ABSTRACT

Modulation of the antiviral innate immune response has been proposed as a putative cellular target for the development of novel pan-viral therapeutic strategies. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is especially relevant due to its essential role in the regulation of local and systemic inflammation in response to viral infections, being, therefore, a putative therapeutic target. Here, we review the extraordinary diversity of strategies that viruses have evolved to interfere with JAK-STAT signaling, stressing the relevance of this pathway as a putative antiviral target. Moreover, due to the recent remarkable progress on the development of novel JAK inhibitors (JAKi), the current knowledge on its efficacy against distinct viral infections is also discussed. JAKi have a proven efficacy against a broad spectrum of disorders and exhibit safety profiles comparable to biologics, therefore representing good candidates for drug repurposing strategies, including viral infections.


Subject(s)
Janus Kinases/metabolism , STAT Transcription Factors/metabolism , Signal Transduction/drug effects , Virus Diseases/metabolism , Viruses/metabolism , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Humans , Immunity, Innate , Inflammation , Janus Kinase Inhibitors/pharmacology , Janus Kinase Inhibitors/therapeutic use , Janus Kinases/antagonists & inhibitors , Virus Diseases/drug therapy , Virus Diseases/immunology , Viruses/classification , Viruses/drug effects
11.
Nucleic Acids Res ; 50(D1): D817-D827, 2022 01 07.
Article in English | MEDLINE | ID: covidwho-1493884

ABSTRACT

Virus infections are huge threats to living organisms and cause many diseases, such as COVID-19 caused by SARS-CoV-2, which has led to millions of deaths. To develop effective strategies to control viral infection, we need to understand its molecular events in host cells. Virus related functional genomic datasets are growing rapidly, however, an integrative platform for systematically investigating host responses to viruses is missing. Here, we developed a user-friendly multi-omics portal of viral infection named as MVIP (https://mvip.whu.edu.cn/). We manually collected available high-throughput sequencing data under viral infection, and unified their detailed metadata including virus, host species, infection time, assay, and target, etc. We processed multi-layered omics data of more than 4900 viral infected samples from 77 viruses and 33 host species with standard pipelines, including RNA-seq, ChIP-seq, and CLIP-seq, etc. In addition, we integrated these genome-wide signals into customized genome browsers, and developed multiple dynamic charts to exhibit the information, such as time-course dynamic and differential gene expression profiles, alternative splicing changes and enriched GO/KEGG terms. Furthermore, we implemented several tools for efficiently mining the virus-host interactions by virus, host and genes. MVIP would help users to retrieve large-scale functional information and promote the understanding of virus-host interactions.


Subject(s)
Databases, Factual , Host Microbial Interactions , Virus Diseases , Animals , Chromatin Immunoprecipitation Sequencing , Gene Ontology , Genome, Viral , High-Throughput Nucleotide Sequencing , Host Microbial Interactions/genetics , Humans , Metadata , Sequence Analysis, RNA , Software , Transcriptome , User-Computer Interface , Virus Diseases/genetics , Virus Diseases/metabolism , Web Browser
12.
Int J Mol Sci ; 22(21)2021 Oct 27.
Article in English | MEDLINE | ID: covidwho-1487420

ABSTRACT

Tetraspanins are transmembrane glycoproteins that have been shown increasing interest as host factors in infectious diseases. In particular, they were implicated in the pathogenesis of both non-enveloped (human papillomavirus (HPV)) and enveloped (human immunodeficiency virus (HIV), Zika, influenza A virus, (IAV), and coronavirus) viruses through multiple stages of infection, from the initial cell membrane attachment to the syncytium formation and viral particle release. However, the mechanisms by which different tetraspanins mediate their effects vary. This review aimed to compare and contrast the role of tetraspanins in the life cycles of HPV, HIV, Zika, IAV, and coronavirus viruses, which cause the most significant health and economic burdens to society. In doing so, a better understanding of the relative contribution of tetraspanins in virus infection will allow for a more targeted approach in the treatment of these diseases.


Subject(s)
Host-Pathogen Interactions/physiology , Tetraspanins/physiology , Virus Diseases/metabolism , Gene Expression Regulation, Viral , HIV-1/pathogenicity , Humans , Influenza A virus/pathogenicity , Papillomaviridae/pathogenicity , SARS-CoV-2/pathogenicity , Virus Diseases/genetics , Virus Diseases/virology , Virus Internalization , Zika Virus/pathogenicity
13.
Int J Mol Sci ; 22(20)2021 Oct 19.
Article in English | MEDLINE | ID: covidwho-1477961

ABSTRACT

Chronic diseases and viral infections have threatened human life over the ages and constitute the main reason for increasing death globally. The rising burden of these diseases extends to negatively affecting the economy and trading globally, as well as daily life, which requires inexpensive, novel, and safe therapeutics. Therefore, scientists have paid close attention to probiotics as safe remedies to combat these morbidities owing to their health benefits and biotherapeutic effects. Probiotics have been broadly adopted as functional foods, nutraceuticals, and food supplements to improve human health and prevent some morbidity. Intriguingly, recent research indicates that probiotics are a promising solution for treating and prophylactic against certain dangerous diseases. Probiotics could also be associated with their essential role in animating the immune system to fight COVID-19 infection. This comprehensive review concentrates on the newest literature on probiotics and their metabolism in treating life-threatening diseases, including immune disorders, pathogens, inflammatory and allergic diseases, cancer, cardiovascular disease, gastrointestinal dysfunctions, and COVID-19 infection. The recent information in this report will particularly furnish a platform for emerging novel probiotics-based therapeutics as cheap and safe, encouraging researchers and stakeholders to develop innovative treatments based on probiotics to prevent and treat chronic and viral diseases.


Subject(s)
Chronic Disease/therapy , Probiotics/administration & dosage , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/therapy , Fatty Acids, Volatile/metabolism , Gastrointestinal Microbiome , Humans , Immune System/metabolism , Inflammation/metabolism , Inflammation/pathology , Neoplasms/metabolism , Neoplasms/therapy , Virus Diseases/immunology , Virus Diseases/metabolism , Virus Diseases/therapy
14.
JCI Insight ; 6(7)2021 04 08.
Article in English | MEDLINE | ID: covidwho-1472322

ABSTRACT

Oxygen-sensing mechanisms allow cells to adapt and respond to changes in cellular oxygen tension, including hypoxic conditions. Hypoxia-inducible factor (HIF) is a central mediator in this fundamental adaptive response, and has critical functions in normal and disease physiology. Viruses have been shown to manipulate HIFs during their life cycle to facilitate replication and invasion. Conversely, HIFs are also implicated in the development of the host immune system and response to viral infections. Here, we highlight the recent revelations of host-pathogen interactions that involve the hypoxic response pathway and the role of HIF in emerging viral infectious diseases, as well as discussing potential antiviral therapeutic strategies targeting the HIF signaling axis.


Subject(s)
Antiviral Agents/pharmacology , Host-Pathogen Interactions/physiology , Virus Diseases/metabolism , Virus Diseases/virology , Host-Pathogen Interactions/drug effects , Humans , Hypoxia , Hypoxia-Inducible Factor 1/metabolism , Virus Diseases/drug therapy , Virus Diseases/immunology
15.
Front Immunol ; 12: 701443, 2021.
Article in English | MEDLINE | ID: covidwho-1470757

ABSTRACT

The airway mucus barrier is a primary defensive layer at the airway surface. Mucins are the major structural components of airway mucus that protect the respiratory tract. Respiratory viruses invade human airways and often induce abnormal mucin overproduction and airway mucus secretion, leading to airway obstruction and disease. The mechanism underlying the virus-induced abnormal airway mucus secretion has not been fully studied so far. Understanding the mechanisms by which viruses induce airway mucus hypersecretion may open new avenues to treatment. In this article, we elaborate the clinical and experimental evidence that respiratory viruses cause abnormal airway mucus secretion, review the underlying mechanisms, and also discuss the current research advance as well as potential strategies to treat the abnormal airway mucus secretion caused by SARS-CoV-2.


Subject(s)
Mucus/metabolism , Virus Diseases/metabolism , Animals , Humans , Respiratory System/metabolism
16.
Front Immunol ; 12: 624293, 2021.
Article in English | MEDLINE | ID: covidwho-1394756

ABSTRACT

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, which interacts with a wide range of organic molecules of endogenous and exogenous origin, including environmental pollutants, tryptophan metabolites, and microbial metabolites. The activation of AHR by these agonists drives its translocation into the nucleus where it controls the expression of a large number of target genes that include the AHR repressor (AHRR), detoxifying monooxygenases (CYP1A1 and CYP1B1), and cytokines. Recent advances reveal that AHR signaling modulates aspects of the intrinsic, innate and adaptive immune response to diverse microorganisms. This review will focus on the increasing evidence supporting a role for AHR as a modulator of the host response to viral infection.


Subject(s)
Adaptive Immunity , Immunity, Innate , Receptors, Aryl Hydrocarbon/metabolism , Virus Diseases/virology , Viruses/immunology , Active Transport, Cell Nucleus , Animals , Gene Expression Regulation , Host-Pathogen Interactions , Humans , Ligands , Signal Transduction , Virus Diseases/genetics , Virus Diseases/immunology , Virus Diseases/metabolism , Viruses/genetics , Viruses/pathogenicity
17.
Viruses ; 13(5)2021 05 04.
Article in English | MEDLINE | ID: covidwho-1383920

ABSTRACT

Viral infections are responsible for several chronic and acute diseases in both humans and animals. Despite the incredible progress in human medicine, several viral diseases, such as acquired immunodeficiency syndrome, respiratory syndromes, and hepatitis, are still associated with high morbidity and mortality rates in humans. Natural products from plants or other organisms are a rich source of structurally novel chemical compounds including antivirals. Indeed, in traditional medicine, many pathological conditions have been treated using plant-derived medicines. Thus, the identification of novel alternative antiviral agents is of critical importance. In this review, we summarize novel phytochemicals with antiviral activity against human viruses and their potential application in treating or preventing viral disease.


Subject(s)
Antiviral Agents/pharmacology , Biological Products/pharmacology , Drug Discovery , Animals , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , Biological Products/chemistry , Biological Products/therapeutic use , DNA Viruses/drug effects , DNA Viruses/physiology , Drug Development , Host-Pathogen Interactions/drug effects , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/immunology , Humans , RNA Viruses/drug effects , RNA Viruses/physiology , Virus Diseases/diagnosis , Virus Diseases/drug therapy , Virus Diseases/etiology , Virus Diseases/metabolism , Virus Replication/drug effects
18.
Biomed Pharmacother ; 140: 111596, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1385083

ABSTRACT

Flavonoids are natural phytochemicals known for their antiviral activity. The flavonoids acts at different stages of viral infection, such as viral entrance, replication and translation of proteins. Viruses cause various diseases such as SARS, Hepatitis, AIDS, Flu, Herpes, etc. These, and many more viral diseases, are prevalent in the world, and some (i.e. SARS-CoV-2) are causing global chaos. Despite much struggle, effective treatments for these viral diseases are not available. The flavonoid class of phytochemicals has a vast number of medicinally active compounds, many of which are studied for their potential antiviral activity against different DNA and RNA viruses. Here, we reviewed many flavonoids that showed antiviral activities in different testing environments such as in vitro, in vivo (mice model) and in silico. Some flavonoids had stronger inhibitory activities, showed no toxicity & the cell proliferation at the tested doses are not affected. Some of the flavonoids used in the in vivo studies also protected the tested mice prophylactically from lethal doses of virus, and effectively prevented viral infection. The glycosides of some of the flavonoids increased the solubility of some flavonoids, and therefore showed increased antiviral activity as compared to the non-glycoside form of that flavonoid. These phytochemicals are active against different disease-causing viruses, and inhibited the viruses by targeting the viral infections at multiple stages. Some of the flavonoids showed more potent antiviral activity than the market available drugs used to treat viral infections.


Subject(s)
Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Flavonoids/pharmacology , Flavonoids/therapeutic use , Virus Diseases/drug therapy , Viruses/drug effects , Animals , Cell Proliferation/drug effects , Glycosides/metabolism , Humans , Virus Diseases/metabolism
19.
J Neurovirol ; 27(4): 531-541, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1384682

ABSTRACT

The conjugation of small ubiquitin-like modifier (SUMO) proteins to substrates is a well-described post-translational modification that regulates protein activity, subcellular localization, and protein-protein interactions for a variety of downstream cellular activities. Several studies describe SUMOylation as an essential post-translational modification for successful viral infection across a broad range of viruses, including RNA and DNA viruses, both enveloped and un-enveloped. These viruses include but are not limited to herpes viruses, human immunodeficiency virus-1, and coronaviruses. In addition to the SUMOylation of viral proteins during infection, evidence shows that viruses manipulate the SUMO pathway for host protein SUMOylation. SUMOylation of host and viral proteins greatly impacts host innate immunity through viral manipulation of the host SUMOylation machinery to promote viral replication and pathogenesis. Other post-translational modifications like phosphorylation can also modulate SUMO function. For example, phosphorylation of COUP-TF interacting protein 2 (CTIP2) leads to its SUMOylation and subsequent proteasomal degradation. The SUMOylation of CTIP2 and subsequent degradation prevents CTIP2-mediated recruitment of a multi-enzymatic complex to the HIV-1 promoter that usually prevents the transcription of integrated viral DNA. Thus, the "SUMO switch" could have implications for CTIP2-mediated transcriptional repression of HIV-1 in latency and viral persistence. In this review, we describe the consequences of SUMO in innate immunity and then focus on the various ways that viral pathogens have evolved to hijack the conserved SUMO machinery. Increased understanding of the many roles of SUMOylation in viral infections can lead to novel insight into the regulation of viral pathogenesis with the potential to uncover new targets for antiviral therapies.


Subject(s)
Host-Pathogen Interactions/physiology , Immunity, Innate/physiology , Sumoylation/physiology , Virus Diseases/immunology , Virus Diseases/metabolism , Animals , Humans , Protein Processing, Post-Translational , SUMO-1 Protein/immunology , SUMO-1 Protein/metabolism
20.
Int J Mol Sci ; 22(17)2021 Aug 29.
Article in English | MEDLINE | ID: covidwho-1374429

ABSTRACT

Heat shock proteins (HSPs) are a large group of chaperones found in most eukaryotes and bacteria. They are responsible for the correct protein folding, protection of the cell against stressors, presenting immune and inflammatory cytokines; furthermore, they are important factors in regulating cell differentiation, survival and death. Although the biological function of HSPs is to maintain cell homeostasis, some of them can be used by viruses both to fold their proteins and increase the chances of survival in unfavorable host conditions. Folding viral proteins as well as replicating many different viruses are carried out by, among others, proteins from the HSP70 and HSP90 families. In some cases, the HSP70 family proteins directly interact with viral polymerase to enhance viral replication or they can facilitate the formation of a viral replication complex and/or maintain the stability of complex proteins. It is known that HSP90 is important for the expression of viral genes at both the transcriptional and the translational levels. Both of these HSPs can form a complex with HSP90 and, consequently, facilitate the entry of the virus into the cell. Current studies have shown the biological significance of HSPs in the course of infection SARS-CoV-2. A comprehensive understanding of chaperone use during viral infection will provide new insight into viral replication mechanisms and therapeutic potential. The aim of this study is to describe the molecular basis of HSP70 and HSP90 participation in some viral infections and the potential use of these proteins in antiviral therapy.


Subject(s)
HSP70 Heat-Shock Proteins/metabolism , HSP90 Heat-Shock Proteins/metabolism , Virus Diseases/pathology , COVID-19/metabolism , COVID-19/pathology , COVID-19/virology , DNA Viruses/physiology , Humans , Protein Isoforms/metabolism , RNA Viruses/physiology , SARS-CoV-2/isolation & purification , Virus Diseases/metabolism , Virus Diseases/virology
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