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1.
Front Cell Infect Microbiol ; 12: 1009328, 2022.
Article in English | MEDLINE | ID: covidwho-2198710

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China in December 2019 and caused a global pandemic resulting in millions of deaths and tens of millions of patients positive tests. While studies have shown a D614G mutation in the viral spike protein are more transmissible, the effects of this and other mutations on the host response, especially at the cellular level, are yet to be fully elucidated. In this experiment we infected normal human bronchial epithelial (NHBE) cells with the Washington (D614) strain or the New York (G614) strains of SARS-CoV-2. We generated RNA sequencing data at 6, 12, and 24 hours post-infection (hpi) to improve our understanding of how the intracellular host response differs between infections with these two strains. We analyzed these data with a bioinformatics pipeline that identifies differentially expressed genes (DEGs), enriched Gene Ontology (GO) terms and dysregulated signaling pathways. We detected over 2,000 DEGs, over 600 GO terms, and 29 affected pathways between the two infections. Many of these entities play a role in immune signaling and response. A comparison between strains and time points showed a higher similarity between matched time points than across different time points with the same strain in DEGs and affected pathways, but found more similarity between strains across different time points when looking at GO terms. A comparison of the affected pathways showed that the 24hpi samples of the New York strain were more similar to the 12hpi samples of the Washington strain, with a large number of pathways related to translation being inhibited in both strains. These results suggest that the various mutations contained in the genome of these two viral isolates may cause distinct effects on the host transcriptional response in infected host cells, especially relating to how quickly translation is dysregulated after infection. This comparison of the intracellular host response to infection with these two SARS-CoV-2 isolates suggest that some of the mechanisms associated with more severe disease from these viruses could include virus replication, metal ion usage, host translation shutoff, host transcript stability, and immune inhibition.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , New York , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Viral Proteins , Washington
2.
Structure ; 28(8): 874-878, 2020 08 04.
Article in English | MEDLINE | ID: covidwho-2132441

ABSTRACT

During global pandemics, the spread of information needs to be faster than the spread of the virus in order to ensure the health and safety of human populations worldwide. In our current crisis, the demand for SARS-CoV-2 drugs and vaccines highlights the importance of biological targets and their three-dimensional shape. In particular, structural biology as a field was poised to quickly respond to crises due to previous experience and expertise and because of its early adoption of open access practices.


Subject(s)
Betacoronavirus/chemistry , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Viral Proteins/chemistry , COVID-19 , Coronavirus 3C Proteases , Coronavirus RNA-Dependent RNA Polymerase , Cysteine Endopeptidases/chemistry , Databases, Protein , Humans , Models, Molecular , Molecular Biology , Protein Conformation , RNA-Dependent RNA Polymerase/chemistry , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/chemistry , Viral Nonstructural Proteins/chemistry
3.
Front Immunol ; 13: 940756, 2022.
Article in English | MEDLINE | ID: covidwho-2141958

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evades the host immune system through a variety of regulatory mechanisms. The genome of SARS-CoV-2 encodes 16 non-structural proteins (NSPs), four structural proteins, and nine accessory proteins that play indispensable roles to suppress the production and signaling of type I and III interferons (IFNs). In this review, we discussed the functions and the underlying mechanisms of different proteins of SARS-CoV-2 that evade the host immune system by suppressing the IFN-ß production and TANK-binding kinase 1 (TBK1)/interferon regulatory factor 3 (IRF3)/signal transducer and activator of transcription (STAT)1 and STAT2 phosphorylation. We also described different viral proteins inhibiting the nuclear translocation of IRF3, nuclear factor-κB (NF-κB), and STATs. To date, the following proteins of SARS-CoV-2 including NSP1, NSP6, NSP8, NSP12, NSP13, NSP14, NSP15, open reading frame (ORF)3a, ORF6, ORF8, ORF9b, ORF10, and Membrane (M) protein have been well studied. However, the detailed mechanisms of immune evasion by NSP5, ORF3b, ORF9c, and Nucleocapsid (N) proteins are not well elucidated. Additionally, we also elaborated the perspectives of SARS-CoV-2 proteins.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Immune Evasion , Interferons/metabolism , Viral Proteins
4.
Sci Rep ; 12(1): 19977, 2022 Nov 20.
Article in English | MEDLINE | ID: covidwho-2133615

ABSTRACT

Metabolomic analysis of blood plasma samples from COVID-19 patients is a promising approach allowing for the evaluation of disease progression. We performed the metabolomic analysis of plasma samples of 30 COVID-19 patients and the 19 controls using the high-performance liquid chromatography (HPLC) coupled with tandem mass spectrometric detection (LC-MS/MS). In our analysis, we identified 103 metabolites enriched in KEGG metabolic pathways such as amino acid metabolism and the biosynthesis of aminoacyl-tRNAs, which differed significantly between the COVID-19 patients and the controls. Using ANDSystem software, we performed the reconstruction of gene networks describing the potential genetic regulation of metabolic pathways perturbed in COVID-19 patients by SARS-CoV-2 proteins. The nonstructural proteins of SARS-CoV-2 (orf8 and nsp5) and structural protein E were involved in the greater number of regulatory pathways. The reconstructed gene networks suggest the hypotheses on the molecular mechanisms of virus-host interactions in COVID-19 pathology and provide a basis for the further experimental and computer studies of the regulation of metabolic pathways by SARS-CoV-2 proteins. Our metabolomic analysis suggests the need for nonstructural protein-based vaccines and the control strategy to reduce the disease progression of COVID-19.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , Gene Regulatory Networks , Chromatography, Liquid , Tandem Mass Spectrometry , Plasma , Viral Proteins/genetics , Disease Progression
5.
Int J Mol Sci ; 23(22)2022 Nov 17.
Article in English | MEDLINE | ID: covidwho-2116111

ABSTRACT

COVID-19 is a disease caused by a novel zoonotic germ known as SARS-CoV-2 coronavirus [...].


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Viral Proteins , Biomarkers , Genetic Variation
6.
Viruses ; 14(11)2022 Nov 16.
Article in English | MEDLINE | ID: covidwho-2116033

ABSTRACT

The recent outbreak of Monkeypox virus requires the development of a vaccine specifically directed against this virus as quickly as possible. We propose here a new strategy based on a two-step analysis combining (i) the search for binding domains of viral proteins to gangliosides present in lipid rafts of host cells, and (ii) B epitope predictions. Based on previous studies of HIV and SARS-CoV-2 proteins, we show that the Monkeypox virus cell surface-binding protein E8L possesses a ganglioside-binding motif consisting of several subsites forming a ring structure. The binding of the E8L protein to a cluster of gangliosides GM1 mimicking a lipid raft domain is driven by both shape and electrostatic surface potential complementarities. An induced-fit mechanism unmasks selected amino acid side chains of the motif without significantly affecting the secondary structure of the protein. The ganglioside-binding motif overlaps three potential linear B epitopes that are well exposed on the unbound E8L surface that faces the host cell membrane. This situation is ideal for generating neutralizing antibodies. We thus suggest using these three sequences derived from the E8L protein as immunogens in a vaccine formulation (recombinant protein, synthetic peptides or genetically based) specific for Monkeypox virus. This lipid raft/ganglioside-based strategy could be used for developing therapeutic and vaccine responses to future virus outbreaks, in parallel to existing solutions.


Subject(s)
Monkeypox virus , Viral Proteins , Epitopes/chemistry , Gangliosides , Monkeypox , Monkeypox virus/chemistry , Viral Proteins/chemistry
7.
Science ; 378(6616): 128-131, 2022 10 14.
Article in English | MEDLINE | ID: covidwho-2114710

ABSTRACT

SARS-CoV-2 wields versatile proteins to foil our immune system's counterattack.


Subject(s)
COVID-19 , SARS-CoV-2 , Viral Proteins , Humans , COVID-19/immunology , SARS-CoV-2/immunology , Viral Proteins/immunology
8.
Front Immunol ; 13: 968981, 2022.
Article in English | MEDLINE | ID: covidwho-2114656

ABSTRACT

Background: The systemic inflammatory response post-SARS-CoV-2 infection increases pro-inflammatory cytokine production, multi-organ damage, and mortality rates. Mast cells (MC) modulate thrombo-inflammatory disease progression (e.g., deep vein thrombosis) and the inflammatory response post-infection. Objective: To enhance our understanding of the contribution of MC and their proteases in SARS-CoV-2 infection and the pathogenesis of the disease, which might help to identify novel therapeutic targets. Methods: MC proteases chymase (CMA1), carboxypeptidase A3 (CPA3), and tryptase beta 2 (TPSB2), as well as cytokine levels, were measured in the serum of 60 patients with SARS-CoV-2 infection (30 moderate and 30 severe; severity of the disease assessed by chest CT) and 17 healthy controls by ELISA. MC number and degranulation were quantified by immunofluorescent staining for tryptase in lung autopsies of patients deceased from either SARS-CoV-2 infection or unrelated reasons (control). Immortalized human FcεR1+c-Kit+ LUVA MC were infected with SARS-CoV-2, or treated with its viral proteins, to assess direct MC activation by flow cytometry. Results: The levels of all three proteases were increased in the serum of patients with COVID-19, and strongly correlated with clinical severity. The density of degranulated MC in COVID-19 lung autopsies was increased compared to control lungs. The total number of released granules and the number of granules per each MC were elevated and positively correlated with von Willebrand factor levels in the lung. SARS-CoV-2 or its viral proteins spike and nucleocapsid did not induce activation or degranulation of LUVA MC in vitro. Conclusion: In this study, we demonstrate that SARS-CoV-2 is strongly associated with activation of MC, which likely occurs indirectly, driven by the inflammatory response. The results suggest that plasma MC protease levels could predict the disease course, and that severe COVID-19 patients might benefit from including MC-stabilizing drugs in the treatment scheme.


Subject(s)
COVID-19 , Carboxypeptidases , Chymases/metabolism , Cytokines , Humans , Mast Cells/metabolism , SARS-CoV-2 , Tryptases/metabolism , Viral Proteins , von Willebrand Factor
9.
J Infect ; 85(4): 365-373, 2022 10.
Article in English | MEDLINE | ID: covidwho-2121901

ABSTRACT

Cyclophilins (Cyps) are a subgroup of peptidyl-prolyl cis-trans isomerases (PPIases) that contain a highly conserved domain of PPIases. Sixteen Cyps have been identified in humans, among which the functions of five classical Cyp subtypes (CypA, B, C, D, and 40) have been studied in more detail. Cyps are widely expressed in almost all human tissues and are involved in several intracellular signaling pathways such as oxidative stress, mitochondrial dysfunction, cell migration, and apoptosis. Several studies have also demonstrated that Cyps play an important role in the development of cardiovascular diseases, neurodegeneration, cancer, and other diseases. However, as regulators of intercellular communication, Cyps have increasingly attracted attention as a result of their implications in viral infection. The specific motifs of Cyps can be targeted by viral proteins and thus promote either a viral infection or an antiviral response. This review highlights the present understanding of Cyps in viral infection and immune response. These effects will facilitate revealing the molecular mechanisms of several diseases induced by viruses and may provide novel insight into the development of corresponding drug-based treatment methods.


Subject(s)
Cyclophilins , Virus Diseases , Cyclophilins/metabolism , Humans , Immunity , Signal Transduction , Viral Proteins
12.
Biomolecules ; 12(11)2022 Nov 12.
Article in English | MEDLINE | ID: covidwho-2109925

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently widespread throughout the world, accompanied by a rising number of people infected and breakthrough infection of variants, which make the virus highly transmissible and replicable. A comprehensive understanding of the molecular virological events and induced immunological features during SARS-CoV-2 replication can provide reliable targets for vaccine and drug development. Among the potential targets, subgenomic RNAs and their encoded proteins involved in the life cycle of SARS-CoV-2 are extremely important in viral duplication and pathogenesis. Subgenomic RNAs employ a range of coping strategies to evade immune surveillance from replication to translation, which allows RNAs to synthesize quickly, encode structural proteins efficiently and complete the entire process of virus replication and assembly successfully. This review focuses on the characteristics and functions of SARS-CoV-2 subgenomic RNAs and their encoded proteins and explores in depth the role of subgenomic RNAs in the replication and infection of host cells to provide important clues to the mechanism of COVID-19 pathogenesis.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , RNA , Virus Replication/genetics , Viral Proteins/metabolism
13.
Biomolecules ; 12(11)2022 Nov 11.
Article in English | MEDLINE | ID: covidwho-2109924

ABSTRACT

Gold compounds have a long tradition in medicine and offer many opportunities for new therapeutic applications. Herein, we evaluated the lead compound Auranofin and five related gold(I) complexes as possible inhibitors of SARS-CoV-2 Main Protease (SARS-CoV-2 Mpro), a validated drug target for the COVID-19 disease. The investigational panel of gold compounds included Auranofin; three halido analogues, i.e., Au(PEt3)Cl, Au(PEt3)Br, and Au(PEt3)I; and two gold carbene complexes, i.e., Au(NHC)Cl and [Au(NHC)2]PF6. Notably, all these gold compounds, with the only exception of [Au(NHC)2]PF6, turned out to be potent inhibitors of the catalytic activity of SARS-CoV-2 Mpro: the measured Ki values were in the range 2.1-0.4 µM. The reactions of the various gold compounds with SARS-CoV-2 Mpro were subsequently investigated through electrospray ionization (ESI) mass spectrometry (MS) upon a careful optimization of the experimental conditions; the ESI MS spectra provided clear evidence for the formation of tight metallodrug-protein adducts and for the coordination of well defined gold-containing fragments to the SARS-CoV-2 Mpro, again with the only exception of [Au(NHC)2]PF6, The metal-protein stoichiometry was unambiguously determined for the resulting species. The crystal structures of the metallodrug- Mpro adducts were solved in the case of Au(PEt3)Br and Au(NHC)Cl. These crystal structures show that gold coordination occurs at the level of catalytic Cys 145 in the case of Au(NHC)Cl and at the level of both Cys 145 and Cys 156 for Au(PEt3)Br. Tight coordination of gold atoms to functionally relevant cysteine residues is believed to represent the true molecular basis of strong enzyme inhibition.


Subject(s)
Auranofin , COVID-19 , Humans , Auranofin/pharmacology , Viral Proteins/chemistry , SARS-CoV-2 , COVID-19/drug therapy , Gold Compounds/pharmacology , Cysteine , Gold/pharmacology
14.
RMD Open ; 8(2)2022 10.
Article in English | MEDLINE | ID: covidwho-2088878

ABSTRACT

OBJECTIVES: To correlate immune responses following a two-dose regimen of mRNA anti-SARS-CoV-2 vaccines in patients with rheumatoid arthritis (RA) to the development of a potent neutralising antiviral activity. METHODS: The RECOVER study was a prospective, monocentric study including patients with RA and healthy controls (HCs). Assessments were performed before, and 3, 6, 12 and 24 weeks, after the first vaccine dose, respectively, and included IgG, IgA and IgM responses (against receptor binding domain, S1, S2, N), IFN-γ ELISpots as well as neutralisation assays. RESULTS: In patients with RA, IgG responses developed slower with lower peak titres compared with HC. Potent neutralising activity assessed by a SARS-CoV-2 pseudovirus neutralisation assay after 12 weeks was observed in all 21 HCs, and in 60.3% of 73 patients with RA. A significant correlation between peak anti-S IgG levels 2 weeks after the second vaccine dose and potent neutralising activity against SARS-CoV-2 was observed at weeks 12 and 24. The analysis of IgG, IgA and IgM isotype responses to different viral proteins demonstrated a delay in IgG but not in IgA and IgM responses. T cell responses were comparable in HC and patients with RA but declined earlier in patients with RA. CONCLUSION: In patients with RA, vaccine-induced IgG antibody levels were diminished, while IgA and IgM responses persisted, indicating a delayed isotype switch. Anti-S IgG levels 2 weeks after the second vaccine dose correlate with the development of a potent neutralising activity after 12 and 24 weeks and may allow to identify patients who might benefit from additional vaccine doses or prophylactic regimen.


Subject(s)
Arthritis, Rheumatoid , COVID-19 , Humans , SARS-CoV-2 , Immunoglobulin A , Prospective Studies , COVID-19/prevention & control , Immunoglobulin G , Immunoglobulin M , Antiviral Agents , Viral Proteins , RNA, Messenger
15.
BMC Med ; 20(1): 359, 2022 10 21.
Article in English | MEDLINE | ID: covidwho-2079420

ABSTRACT

BACKGROUND: The severe fever with thrombocytopenia syndrome disease (SFTS), caused by the novel tick-borne SFTS virus (SFTSV), was listed among the top 10 priority infectious disease by World Health Organization due to the high fatality rate of 5-30% and the lack of effective antiviral drugs and vaccines and therefore raised the urgent need to develop effective anti-SFTSV drugs to improve disease treatment. METHODS: The antiviral drugs to inhibit SFTSV infection were identified by screening the library containing 1340 FDA-approved drugs using the SFTSV infection assays in vitro. The inhibitory effect on virus entry and the process of clathrin-mediated endocytosis under different drug doses was evaluated based on infection assays by qRT-PCR to determine intracellular viral copies, by Western blot to characterize viral protein expression in cells, and by immunofluorescence assays (IFAs) to determine virus infection efficiencies. The therapeutic effect was investigated in type I interferon receptor defective A129 mice in vivo with SFTSV infection, from which lesions and infection in tissues caused by SFTSV infection were assessed by H&E staining and immunohistochemical analysis. RESULTS: Six drugs were identified as exerting inhibitory effects against SFTSV infection, of which anidulafungin, an antifungal drug of the echinocandin family, has a strong inhibitory effect on SFTSV entry. It suppresses SFTSV internalization by impairing the late endosome maturation and decreasing virus fusion with the membrane. SFTSV-infected A129 mice had relieving symptoms, reduced tissue lesions, and improved disease outcomes following anidulafungin treatment. Moreover, anidulafungin exerts an antiviral effect in inhibiting the entry of other viruses including SARS-CoV-2, SFTSV-related Guertu virus and Heartland virus, Crimean-Congo hemorrhagic fever virus, Zika virus, and Herpes simplex virus 1. CONCLUSIONS: The results demonstrated that the antifungal drug, anidulafungin, could effectively inhibit virus infection by interfering with virus entry, suggesting it may be utilized for the clinical treatment of infectious viral diseases, in addition to its FDA-approved use as an antifungal. The findings also suggested to further evaluate the anti-viral effects of echinocandins and their clinical importance for patients with infection of viruses, which may promote therapeutic strategies as well as treatments and improve outcomes pertaining to various viral and fungal diseases.


Subject(s)
Anidulafungin , Bunyaviridae Infections , Virus Diseases , Animals , Mice , Anidulafungin/pharmacology , Anidulafungin/therapeutic use , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Bunyaviridae Infections/drug therapy , Clathrin , Receptor, Interferon alpha-beta , SARS-CoV-2 , Viral Proteins , Virus Diseases/drug therapy
16.
Viruses ; 14(10)2022 10 16.
Article in English | MEDLINE | ID: covidwho-2071840

ABSTRACT

Host-virus protein interactions are critical for intracellular viral propagation. Understanding the interactions between cellular and viral proteins may help us develop new antiviral strategies. Porcine epidemic diarrhea virus (PEDV) is a highly contagious coronavirus that causes severe damage to the global swine industry. Here, we employed co-immunoprecipitation and liquid chromatography-mass spectrometry to characterize 426 unique PEDV nucleocapsid (N) protein-binding proteins in infected Vero cells. A protein-protein interaction network (PPI) was created, and gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) database analyses revealed that the PEDV N-bound proteins belong to different cellular pathways, such as nucleic acid binding, ribonucleoprotein complex binding, RNA methyltransferase, and polymerase activities. Interactions of the PEDV N protein with 11 putative proteins: tripartite motif containing 21, DEAD-box RNA helicase 24, G3BP stress granule assembly factor 1, heat shock protein family A member 8, heat shock protein 90 alpha family class B member 1, YTH domain containing 1, nucleolin, Y-box binding protein 1, vimentin, heterogeneous nuclear ribonucleoprotein A2/B1, and karyopherin subunit alpha 1, were further confirmed by in vitro co-immunoprecipitation assay. In summary, studying an interaction network can facilitate the identification of antiviral therapeutic strategies and novel targets for PEDV infection.


Subject(s)
Coronavirus Infections , Nucleic Acids , Porcine epidemic diarrhea virus , Swine Diseases , Chlorocebus aethiops , Swine , Animals , Porcine epidemic diarrhea virus/genetics , Vimentin/metabolism , Vero Cells , Nucleocapsid/metabolism , Nucleocapsid Proteins/genetics , Viral Proteins/metabolism , Coronavirus Infections/metabolism , Antiviral Agents/metabolism , RNA/metabolism , Heat-Shock Proteins/metabolism , Methyltransferases/metabolism , Heterogeneous-Nuclear Ribonucleoproteins/metabolism , DEAD-box RNA Helicases/metabolism , Ribonucleoproteins/metabolism , Karyopherins/metabolism , Nucleic Acids/metabolism
17.
Viruses ; 14(10)2022 10 07.
Article in English | MEDLINE | ID: covidwho-2066560

ABSTRACT

The Coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in a major health crisis worldwide with its continuously emerging new strains, resulting in new viral variants that drive "waves" of infection. PCR or antigen detection assays have been routinely used to detect clinical infections; however, the emergence of these newer strains has presented challenges in detection. One of the alternatives has been to detect and characterize variant-specific peptide sequences from viral proteins using mass spectrometry (MS)-based methods. MS methods can potentially help in both diagnostics and vaccine development by understanding the dynamic changes in the viral proteome associated with specific strains and infection waves. In this study, we developed an accessible, flexible, and shareable bioinformatics workflow that was implemented in the Galaxy Platform to detect variant-specific peptide sequences from MS data derived from the clinical samples. We demonstrated the utility of the workflow by characterizing published clinical data from across the world during various pandemic waves. Our analysis identified six SARS-CoV-2 variant-specific peptides suitable for confident detection by MS in commonly collected clinical samples.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , COVID-19/diagnosis , Proteome , Peptides , Viral Proteins/genetics
18.
Int J Mol Sci ; 23(19)2022 Sep 30.
Article in English | MEDLINE | ID: covidwho-2066131

ABSTRACT

The World Health Organization declared monkeypox a global public health emergency on 23 July 2022. This disease was caused by the monkeypox virus (MPXV), which was first identified in 1958 in Denmark. The MPXV is a member of the Poxviridae family, the Chordopoxvirinae subfamily, and the genus Orthopoxvirus, which share high similarities with the vaccinia virus (the virus used to produce the smallpox vaccine). For the initial stage of infection, the MPXV needs to attach to the human cell surface glycosaminoglycan (GAG) adhesion molecules using its E8 protein. However, up until now, neither a structure for the MPXV E8 protein nor a specific cure for the MPXV exists. This study aimed to search for small molecules that inhibit the MPXV E8 protein, using computational approaches. In this study, a high-quality three-dimensional structure of the MPXV E8 protein was retrieved by homology modeling using the AlphaFold deep learning server. Subsequent molecular docking and molecular dynamics simulations (MDs) for a cumulative duration of 2.1 microseconds revealed that ZINC003977803 (Diosmin) and ZINC008215434 (Flavin adenine dinucleotide-FAD) could be potential inhibitors against the E8 protein with the MM/GBSA binding free energies of -38.19 ± 9.69 and -35.59 ± 7.65 kcal·mol-1, respectively.


Subject(s)
Diosmin , Monkeypox , Smallpox Vaccine , Flavin-Adenine Dinucleotide , Glycosaminoglycans , Humans , Molecular Docking Simulation , Monkeypox/prevention & control , Monkeypox virus , Viral Proteins
19.
Front Immunol ; 13: 989298, 2022.
Article in English | MEDLINE | ID: covidwho-2065518

ABSTRACT

The heterogeneous nuclear ribonucleoproteins (hnRNPs) are a diverse family of RNA binding proteins that are implicated in RNA metabolism, such as alternative splicing, mRNA stabilization and translational regulation. According to their different cellular localization, hnRNPs display multiple functions. Most hnRNPs were predominantly located in the nucleus, but some of them could redistribute to the cytoplasm during virus infection. HnRNPs consist of different domains and motifs that enable these proteins to recognize predetermined nucleotide sequences. In the virus-host interactions, hnRNPs specifically bind to viral RNA or proteins. And some of the viral protein-hnRNP interactions require the viral RNA or other host factors as the intermediate. Through various mechanisms, hnRNPs could regulate viral translation, viral genome replication, the switch of translation to replication and virion release. This review highlights the common features and the distinguish roles of hnRNPs in the life cycle of positive single-stranded RNA viruses.


Subject(s)
Heterogeneous-Nuclear Ribonucleoproteins , Positive-Strand RNA Viruses , Animals , Heterogeneous-Nuclear Ribonucleoproteins/genetics , Heterogeneous-Nuclear Ribonucleoproteins/metabolism , Life Cycle Stages , RNA, Messenger/metabolism , RNA, Viral/genetics , RNA, Viral/metabolism , RNA-Binding Proteins , Viral Proteins/metabolism
20.
Sci Rep ; 12(1): 16929, 2022 Oct 08.
Article in English | MEDLINE | ID: covidwho-2062268

ABSTRACT

The SARS-CoV-2 pandemic has added new urgency to the study of viral mechanisms of infection. But while vaccines offer a measure of protection against this specific outbreak, a new era of pandemics has been predicted. In addition to this, COVID-19 has drawn attention to post-viral syndromes and the healthcare burden they entail. It seems integral that knowledge of viral mechanisms is increased through as wide a research field as possible. To this end we propose that quantum biology might offer essential new insights into the problem, especially with regards to the important first step of virus-host invasion. Research in quantum biology often centres around energy or charge transfer. While this is predominantly in the context of photosynthesis there has also been some suggestion that cellular receptors such as olfactory or neural receptors might employ vibration assisted electron tunnelling to augment the lock-and-key mechanism. Quantum tunnelling has also been observed in enzyme function. Enzymes are implicated in the invasion of host cells by the SARS-CoV-2 virus. Receptors such as olfactory receptors also appear to be disrupted by COVID-19. Building on these observations we investigate the evidence that quantum tunnelling might be important in the context of infection with SARS-CoV-2. We illustrate this with a simple model relating the vibronic mode of, for example, a viral spike protein to the likelihood of charge transfer in an idealised receptor. Our results show a distinct parameter regime in which the vibronic mode of the spike protein enhances electron transfer. With this in mind, novel therapeutics to prevent SARS-CoV-2 transmission could potentially be identified by their vibrational spectra.


Subject(s)
COVID-19 , Receptors, Odorant , Angiotensin-Converting Enzyme 2 , Humans , Receptors, Virus/metabolism , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/metabolism , Viral Proteins
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