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1.
Elife ; 92020 08 17.
Article in English | MEDLINE | ID: covidwho-2155739

ABSTRACT

Temporal inference from laboratory testing results and triangulation with clinical outcomes extracted from unstructured electronic health record (EHR) provider notes is integral to advancing precision medicine. Here, we studied 246 SARS-CoV-2 PCR-positive (COVIDpos) patients and propensity-matched 2460 SARS-CoV-2 PCR-negative (COVIDneg) patients subjected to around 700,000 lab tests cumulatively across 194 assays. Compared to COVIDneg patients at the time of diagnostic testing, COVIDpos patients tended to have higher plasma fibrinogen levels and lower platelet counts. However, as the infection evolves, COVIDpos patients distinctively show declining fibrinogen, increasing platelet counts, and lower white blood cell counts. Augmented curation of EHRs suggests that only a minority of COVIDpos patients develop thromboembolism, and rarely, disseminated intravascular coagulopathy (DIC), with patients generally not displaying platelet reductions typical of consumptive coagulopathies. These temporal trends provide fine-grained resolution into COVID-19 associated coagulopathy (CAC) and set the stage for personalizing thromboprophylaxis.


Subject(s)
Betacoronavirus/isolation & purification , Blood Coagulation Disorders/diagnosis , Blood Coagulation Tests , Blood Coagulation , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Aged , Betacoronavirus/pathogenicity , Biomarkers/blood , Blood Coagulation Disorders/blood , Blood Coagulation Disorders/virology , COVID-19 , COVID-19 Testing , Coronavirus Infections/blood , Coronavirus Infections/virology , Disease Progression , Female , Fibrinogen/metabolism , Host Microbial Interactions , Humans , Leukocyte Count , Longitudinal Studies , Male , Middle Aged , Pandemics , Platelet Count , Pneumonia, Viral/blood , Pneumonia, Viral/virology , Predictive Value of Tests , Reproducibility of Results , Retrospective Studies , SARS-CoV-2 , Time Factors
2.
Viruses ; 14(11)2022 Nov 02.
Article in English | MEDLINE | ID: covidwho-2123861

ABSTRACT

The porcine epidemic diarrhea virus (PEDV) is a member of the coronavirus family, causing deadly watery diarrhea in newborn piglets. The global pandemic of PEDV, with significant morbidity and mortality, poses a huge threat to the swine industry. The currently developed vaccines and drugs are only effective against the classic GI strains that were prevalent before 2010, while there is no effective control against the GII variant strains that are currently a global pandemic. In this review, we summarize the latest progress in the biology of PEDV, including its transmission and origin, structure and function, evolution, and virus-host interaction, in an attempt to find the potential virulence factors influencing PEDV pathogenesis. We conclude with the mechanism by which PEDV components antagonize the immune responses of the virus, and the role of host factors in virus infection. Essentially, this review serves as a valuable reference for the development of attenuated virus vaccines and the potential of host factors as antiviral targets for the prevention and control of PEDV infection.


Subject(s)
Coronavirus Infections , Coronavirus , Porcine epidemic diarrhea virus , Swine Diseases , Animals , Swine , Virulence , Host Microbial Interactions , Coronavirus Infections/epidemiology , Coronavirus Infections/veterinary , Vaccines, Attenuated
3.
Int J Mol Sci ; 23(21)2022 Nov 01.
Article in English | MEDLINE | ID: covidwho-2119021

ABSTRACT

"Omics" is becoming an increasingly recognizable term, even to the general public, as it is used more and more often in everyday scientific research [...].


Subject(s)
Microbiota , Host Microbial Interactions
4.
Front Cell Infect Microbiol ; 12: 1002856, 2022.
Article in English | MEDLINE | ID: covidwho-2065455
5.
Nature ; 610(7931): 381-388, 2022 10.
Article in English | MEDLINE | ID: covidwho-2050416

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged at the end of 2019 and caused the devastating global pandemic of coronavirus disease 2019 (COVID-19), in part because of its ability to effectively suppress host cell responses1-3. In rare cases, viral proteins dampen antiviral responses by mimicking critical regions of human histone proteins4-8, particularly those containing post-translational modifications required for transcriptional regulation9-11. Recent work has demonstrated that SARS-CoV-2 markedly disrupts host cell epigenetic regulation12-14. However, how SARS-CoV-2 controls the host cell epigenome and whether it uses histone mimicry to do so remain unclear. Here we show that the SARS-CoV-2 protein encoded by ORF8 (ORF8) functions as a histone mimic of the ARKS motifs in histone H3 to disrupt host cell epigenetic regulation. ORF8 is associated with chromatin, disrupts regulation of critical histone post-translational modifications and promotes chromatin compaction. Deletion of either the ORF8 gene or the histone mimic site attenuates the ability of SARS-CoV-2 to disrupt host cell chromatin, affects the transcriptional response to infection and attenuates viral genome copy number. These findings demonstrate a new function of ORF8 and a mechanism through which SARS-CoV-2 disrupts host cell epigenetic regulation. Further, this work provides a molecular basis for the finding that SARS-CoV-2 lacking ORF8 is associated with decreased severity of COVID-19.


Subject(s)
COVID-19 , Epigenesis, Genetic , Histones , Host Microbial Interactions , Molecular Mimicry , SARS-CoV-2 , Viral Proteins , COVID-19/genetics , COVID-19/metabolism , COVID-19/virology , Chromatin/genetics , Chromatin/metabolism , Chromatin Assembly and Disassembly , Epigenome/genetics , Histones/chemistry , Histones/metabolism , Humans , SARS-CoV-2/genetics , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Viral Proteins/chemistry , Viral Proteins/genetics , Viral Proteins/metabolism
6.
Biomolecules ; 12(8)2022 07 29.
Article in English | MEDLINE | ID: covidwho-2023131

ABSTRACT

The emerging SARS-CoV and SARS-CoV-2 belong to the family of "common cold" RNA coronaviruses, and they are responsible for the 2003 epidemic and the current pandemic with over 6.3 M deaths worldwide. The ORF3a gene is conserved in both viruses and codes for the accessory protein ORF3a, with unclear functions, possibly related to viral virulence and pathogenesis. The tyrosine-based YXXΦ motif (Φ: bulky hydrophobic residue-L/I/M/V/F) was originally discovered to mediate clathrin-dependent endocytosis of membrane-spanning proteins. Many viruses employ the YXXΦ motif to achieve efficient receptor-guided internalisation in host cells, maintain the structural integrity of their capsids and enhance viral replication. Importantly, this motif has been recently identified on the ORF3a proteins of SARS-CoV and SARS-CoV-2. Given that the ORF3a aa sequence is not fully conserved between the two SARS viruses, we aimed to map in silico structural differences and putative sequence-driven alterations of regulatory elements within and adjacently to the YXXΦ motifs that could predict variations in ORF3a functions. Using robust bioinformatics tools, we investigated the presence of relevant post-translational modifications and the YXXΦ motif involvement in protein-protein interactions. Our study suggests that the predicted YXXΦ-related features may confer specific-yet to be discovered-functions to ORF3a proteins, significant to the new virus and related to enhanced propagation, host immune regulation and virulence.


Subject(s)
COVID-19 , SARS Virus , Host Microbial Interactions , Humans , Peptides , SARS Virus/genetics , SARS-CoV-2
7.
J Virol ; 96(17): e0074122, 2022 09 14.
Article in English | MEDLINE | ID: covidwho-1992937

ABSTRACT

Within the past 2 decades, three highly pathogenic human coronaviruses have emerged, namely, severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The health threats and economic burden posed by these tremendously severe coronaviruses have paved the way for research on their etiology, pathogenesis, and treatment. Compared to SARS-CoV and SARS-CoV-2, MERS-CoV genome encoded fewer accessory proteins, among which the ORF4b protein had anti-immunity ability in both the cytoplasm and nucleus. Our work for the first time revealed that ORF4b protein was unstable in the host cells and could be degraded by the ubiquitin proteasome system. After extensive screenings, it was found that UBR5 (ubiquitin protein ligase E3 component N-recognin 5), a member of the HECT E3 ubiquitin ligases, specifically regulated the ubiquitination and degradation of ORF4b. Similar to ORF4b, UBR5 can also translocate into the nucleus through its nuclear localization signal, enabling it to regulate ORF4b stability in both the cytoplasm and nucleus. Through further experiments, lysine 36 was identified as the ubiquitination site on the ORF4b protein, and this residue was highly conserved in various MERS-CoV strains isolated from different regions. When UBR5 was knocked down, the ability of ORF4b to suppress innate immunity was enhanced and MERS-CoV replication was stronger. As an anti-MERS-CoV host protein, UBR5 targets and degrades ORF4b protein through the ubiquitin proteasome system, thereby attenuating the anti-immunity ability of ORF4b and ultimately inhibiting MERS-CoV immune escape, which is a novel antagonistic mechanism of the host against MERS-CoV infection. IMPORTANCE ORF4b was an accessory protein unique to MERS-CoV and was not present in SARS-CoV and SARS-CoV-2 which can also cause severe respiratory disease. Moreover, ORF4b inhibited the production of antiviral cytokines in both the cytoplasm and the nucleus, which was likely to be associated with the high lethality of MERS-CoV. However, whether the host proteins regulate the function of ORF4b is unknown. Our study first determined that UBR5, a host E3 ligase, was a potential host anti-MERS-CoV protein that could reduce the protein level of ORF4b and diminish its anti-immunity ability by inducing ubiquitination and degradation. Based on the discovery of ORF4b-UBR5, a critical molecular target, further increasing the degradation of ORF4b caused by UBR5 could provide a new strategy for the clinical development of drugs for MERS-CoV.


Subject(s)
Coronavirus Infections , Host Microbial Interactions , Middle East Respiratory Syndrome Coronavirus , Proteolysis , Ubiquitin-Protein Ligases , Ubiquitination , Viral Proteins , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Coronavirus Infections/virology , Cytokines/immunology , Humans , Immunity, Innate , Middle East Respiratory Syndrome Coronavirus/immunology , Middle East Respiratory Syndrome Coronavirus/metabolism , Molecular Targeted Therapy , Proteasome Endopeptidase Complex/metabolism , SARS Virus , SARS-CoV-2 , Ubiquitin-Protein Ligases/metabolism , Ubiquitins/metabolism , Viral Proteins/chemistry , Viral Proteins/metabolism , Virus Replication
8.
Front Immunol ; 13: 939768, 2022.
Article in English | MEDLINE | ID: covidwho-1987496

ABSTRACT

Circular RNAs (circRNAs) as novel regulatory molecules have been recognized in diverse species, including viruses. The virus-derived circRNAs play various roles in the host biological process and the life cycle of the viruses. This review summarized the circRNAs from the DNA and RNA viruses and discussed the biogenesis of viral and host circRNAs, the potential roles of viral circRNAs, and their future perspective. This review will elaborate on new insights gained on viruses encoded circRNAs during virus infection.


Subject(s)
Host Microbial Interactions , RNA, Circular , Host Microbial Interactions/genetics , RNA, Circular/genetics
9.
Nature ; 609(7928): 754-760, 2022 09.
Article in English | MEDLINE | ID: covidwho-1984401

ABSTRACT

Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1-5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.


Subject(s)
COVID-19 , GTPase-Activating Proteins , Genome-Wide Association Study , Guanine Nucleotide Exchange Factors , Host Microbial Interactions , SARS-CoV-2 , Alleles , Animals , COVID-19/complications , COVID-19/genetics , COVID-19/immunology , COVID-19/physiopathology , Disease Models, Animal , GTPase-Activating Proteins/antagonists & inhibitors , GTPase-Activating Proteins/genetics , GTPase-Activating Proteins/metabolism , Genetic Predisposition to Disease , Guanine Nucleotide Exchange Factors/antagonists & inhibitors , Guanine Nucleotide Exchange Factors/genetics , Guanine Nucleotide Exchange Factors/metabolism , Host Microbial Interactions/genetics , Host Microbial Interactions/immunology , Humans , Interferon Type I/genetics , Interferon Type I/immunology , Japan , Lung/pathology , Macrophages , Mesocricetus , Middle Aged , Pneumonia/complications , Pyrazoles/pharmacology , RNA-Seq , SARS-CoV-2/pathogenicity , Viral Load , Weight Loss
10.
STAR Protoc ; 3(3): 101648, 2022 09 16.
Article in English | MEDLINE | ID: covidwho-1967230

ABSTRACT

Here, we describe a bioinformatics pipeline that evaluates the interactions between coagulation-related proteins and genetic variants with SARS-CoV-2 proteins. This pipeline searches for host proteins that may bind to viral protein and identifies and scores the protein genetic variants to predict the disease pathogenesis in specific subpopulations. Additionally, it is able to find structurally similar motifs and identify potential binding sites within the host-viral protein complexes to unveil viral impact on regulated biological processes and/or host-protein impact on viral invasion or reproduction. For complete details on the use and execution of this protocol, please refer to Holcomb et al. (2021).


Subject(s)
COVID-19 , SARS-CoV-2 , Binding Sites , COVID-19/genetics , Host Microbial Interactions , Humans , SARS-CoV-2/genetics , Viral Proteins/genetics
11.
Sci Rep ; 12(1): 11934, 2022 07 13.
Article in English | MEDLINE | ID: covidwho-1931487

ABSTRACT

COVID-19 is a global pandemic impacting the daily living of millions. As variants of the virus evolve, a complete comprehension of the disease and drug targets becomes a decisive duty. The Omicron variant, for example, has a notably high transmission rate verified in 155 countries. We performed integrative transcriptomic and network analyses to identify drug targets and diagnostic biomarkers and repurpose FDA-approved drugs for SARS-CoV-2. Upon the enrichment of 464 differentially expressed genes, pathways regulating the host cell cycle were significant. Regulatory and interaction networks featured hsa-mir-93-5p and hsa-mir-17-5p as blood biomarkers while hsa-mir-15b-5p as an antiviral agent. MYB, RRM2, ERG, CENPF, CIT, and TOP2A are potential drug targets for treatment. HMOX1 is suggested as a prognostic biomarker. Enhancing HMOX1 expression by neem plant extract might be a therapeutic alternative. We constructed a drug-gene network for FDA-approved drugs to be repurposed against the infection. The key drugs retrieved were members of anthracyclines, mitotic inhibitors, anti-tumor antibiotics, and CDK1 inhibitors. Additionally, hydroxyquinone and digitoxin are potent TOP2A inhibitors. Hydroxyurea, cytarabine, gemcitabine, sotalol, and amiodarone can also be redirected against COVID-19. The analysis enforced the repositioning of fluorouracil and doxorubicin, especially that they have multiple drug targets, hence less probability of resistance.


Subject(s)
COVID-19 , MicroRNAs , Biomarkers , COVID-19/drug therapy , Drug Repositioning , Host Microbial Interactions , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , SARS-CoV-2
12.
Microbiol Spectr ; 10(4): e0140522, 2022 08 31.
Article in English | MEDLINE | ID: covidwho-1909614

ABSTRACT

We previously found that a deletion in γ-coronavirus Infectious bronchitis virus (IBV) accessory gene 5a is critical for decreased viral pathogenicity in chickens. Here, we systematically analyzed IBV virus infection: invasion, genome replication, subgenomic mRNA (sgmRNA) synthesis, protein synthesis, and virion release. The ability of the mutant IBV strain rYN-Δ5a to invade susceptible cells was not significantly different from that of parental rYN. However, compared with rYN, the level of sgmRNA synthesis and genome replication after cell entry by rYN-Δ5a was significantly lower in the early stage, resulting in a significantly lower level of nucleoprotein (N) synthesis and a consequent significantly lower number of offspring viruses released into the supernatant. The detected 5a protein was diffusely distributed in the cytoplasm and perinuclear area. We identified 16 differentially expressed host proteins, 8 of which were found to be host nuclear and cytoplasmic transport-related proteins. Coimmunoprecipitation revealed an interaction between hemagglutinin (HA)-tagged TNPO1, TNPO3, XPO1, XPOT, RanBP1, and EIF2B4 proteins and Flag-tagged 5a protein, and laser confocal microscopy confirmed 5a protein colocalization with these proteins, indicating that 5a protein can cause changes in the host protein localization. These host proteins promote the nuclear localization of N proteins, so we believe that 5a protein can hijack host nucleoplasmic transport-related proteins to help N enter the nucleus. This may involve regulating the cell cycle to promote the optimal intracellular conditions for virus assembly or by participating in the regulation of nucleolar function as a strategy to optimize virus replication. IMPORTANCE Coronaviruses (CoVs) have a huge impact on humans and animals. It is important for the prevention and control of the viruses to assess the molecular mechanisms related to virulence attenuation. Here, we systematically analyzed a single cycle of virus infection by γ-CoV IBV lacking accessory protein 5a. We observed that a 5a deletion in the IBV genome affected virus replication and sgmRNA synthesis early in the virus life cycle, leading to decreases in protein synthesis, offspring virus assembly, and virion release in chicken embryonic kidney cells. IBV 5a protein was found to interact with multiple host nuclear and cytoplasmic transport- and translation-related proteins, which can also interact with IBV N and relocate it into the cell nucleus. These findings provide a comprehensive view regarding the importance of IBV accessory protein 5a and an important theoretical basis for studying the interaction between coronavirus and host cell proteins.


Subject(s)
Coronavirus Infections , Infectious bronchitis virus , Poultry Diseases , Virus Diseases , Animals , Chick Embryo , Chickens , Coronavirus Infections/veterinary , Host Microbial Interactions , Infectious bronchitis virus/genetics , Nucleocytoplasmic Transport Proteins/metabolism , Nucleotides/metabolism , Virus Diseases/veterinary , Virus Replication , beta Karyopherins/metabolism
14.
Proc Natl Acad Sci U S A ; 119(28): e2119761119, 2022 07 12.
Article in English | MEDLINE | ID: covidwho-1900767

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein is the prime target for vaccines, diagnostics, and therapeutic antibodies against the virus. While anchored in the viral envelope, for effective virulence, the spike needs to maintain structural flexibility to recognize the host cell surface receptors and bind to them, a property that can heavily depend upon the dynamics of the unresolved domains, most prominently the stalk. Construction of the complete, membrane-bound spike model and the description of its dynamics are critical steps in understanding the inner working of this key element of the viral infection by SARS-CoV-2. Combining homology modeling, protein-protein docking, and molecular dynamics (MD) simulations, we have developed a full spike structure in a native membrane. Multimicrosecond MD simulations of this model, the longest known single trajectory of the full spike, reveal conformational dynamics employed by the protein to explore the surface of the host cell. In agreement with cryogenic electron microscopy (cryo-EM), three flexible hinges in the stalk allow for global conformational heterogeneity of spike in the fully glycosylated system mediated by glycan-glycan and glycan-lipid interactions. The dynamical range of the spike is considerably reduced in its nonglycosylated form, confining the area explored by the spike on the host cell surface. Furthermore, palmitoylation of the membrane domain amplifies the local curvature that may prime the fusion. We show that the identified hinge regions are highly conserved in SARS coronaviruses, highlighting their functional importance in enhancing viral infection, and thereby, provide points for discovery of alternative therapeutics against the virus.


Subject(s)
COVID-19 , Host Microbial Interactions , Protein Processing, Post-Translational , Receptors, Cell Surface , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , COVID-19/virology , Glycosylation , Humans , Polysaccharides , Protein Binding , Receptors, Cell Surface/metabolism , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism
15.
Sci Rep ; 12(1): 9399, 2022 Jun 07.
Article in English | MEDLINE | ID: covidwho-1882769

ABSTRACT

COVID-19, caused by SARS-CoV-2, is a primarily pulmonary disease that can affect several organs, directly or indirectly. To date, there are many questions about the different pathological mechanisms. Here, we generate an approach to identify the cellular-level tropism of SARS-CoV-2 using human proteomics, virus-host interactions, and enrichment analysis. Through a network-based approach, the molecular context was visualized and analyzed. This procedure was also performed for SARS-CoV-1. We obtained proteomes and interactomes from 145 different cells corresponding to 57 different tissues. We discarded the cells without the proteins known for interacting with the virus, such as ACE2 or TMPRSS2. Of the remaining cells, a gradient of susceptibility to infection was observed. In addition, we identified proteins associated with the coagulation cascade that can be directly or indirectly affected by viral proteins. As a whole we identified 55 cells that could be potentially controlled by the virus, with different susceptibilities, mainly being pneumocytes, heart, kidney, liver, or small intestine cells. These results help to explain the molecular context and provide elements for possible treatments in the current situation. This strategy may be useful for other viruses, especially those with limited reported PPI, such as a new virus.


Subject(s)
COVID-19 , SARS-CoV-2 , Angiotensin-Converting Enzyme 2 , Host Microbial Interactions , Humans , Tropism
16.
Curr Opin Virol ; 54: 101229, 2022 06.
Article in English | MEDLINE | ID: covidwho-1881820
17.
J Virol ; 96(12): e0041222, 2022 06 22.
Article in English | MEDLINE | ID: covidwho-1874504

ABSTRACT

SARS-CoV-2 is the causative agent of the ongoing pandemic of coronavirus disease 2019 (COVID-19) and poses a significant threat to global health. N protein (NP), which is a major pathogenic protein among betacoronaviruses, binds to the viral RNA genome to allow viral genome packaging and viral particle release. Recent studies showed that NP antagonizes interferon (IFN) induction and mediates phase separation. Using live SARS-CoV-2 viruses, this study provides solid evidence showing that SARS-CoV-2 NP associates with G3BP1 and G3BP2 in vitro and in vivo. NPSARS-CoV-2 could efficiently suppress G3BP-mediated SG formation and potentiate viral infection by overcoming G3BP1-mediated antiviral innate immunity. G3BP1 conditional knockout mice (g3bp1fl/fL, Sftpc-Cre) exhibit significantly higher lung viral loads after SARS-CoV-2 infection than wild-type mice. Our findings contribute to the growing body of knowledge regarding the pathogenicity of NPSARS-CoV-2 and provide insight into new therapeutics targeting NPSARS-CoV-2. IMPORTANCE In this study, by in vitro assay and live SARS-CoV-2 virus infection, we provide solid evidence that the SARS-CoV-2 NP associates with G3BP1 and G3BP2 in vitro and in vivo. NPSARS-CoV-2 could efficiently suppress G3BP-mediated SG formation and potentiate viral infection by overcoming antiviral innate immunity mediated by G3BP1 in A549 cell lines and G3BP1 conditional knockout mice (g3bp1-cKO) mice, which provide in-depth evidence showing the mechanism underlying NP-related SARS-CoV-2 pathogenesis through G3BPs.


Subject(s)
COVID-19 , Coronavirus Nucleocapsid Proteins , Poly-ADP-Ribose Binding Proteins , SARS-CoV-2 , Virus Replication , Adaptor Proteins, Signal Transducing/metabolism , Animals , COVID-19/immunology , COVID-19/virology , Coronavirus Nucleocapsid Proteins/metabolism , DNA Helicases/metabolism , Host Microbial Interactions/immunology , Mice , Phosphoproteins/metabolism , Poly-ADP-Ribose Binding Proteins/metabolism , RNA Helicases/metabolism , RNA Recognition Motif Proteins/metabolism , RNA-Binding Proteins/metabolism , Stress Granules , Virus Replication/genetics
19.
Adv Protein Chem Struct Biol ; 131: 261-276, 2022.
Article in English | MEDLINE | ID: covidwho-1866754

ABSTRACT

Numerous viruses have evolved mechanisms to inhibit or alter the host cell's apoptotic response as part of their coevolution with their hosts. The analysis of virus-host protein interactions require an in-depth understanding of both the viral and host protein structures and repertoires, as well as evolutionary mechanisms and pertinent biological facts. Throughout the course of a viral infection, there is constant battle for binding between virus and cellular proteins. Exogenous interfaces facilitating viral-host interactions are well known for constantly targeting and suppressing endogenous interfaces mediating intraspecific interactions, such as viral-viral and host-host connections. In these interactions, the protein-protein interactions (PPIs), are mostly shown as networks (protein interaction networks, PINs), with proteins represented as nodes and their interactions represented as edges. Host proteins with a higher degree of connectivity are more likely to interact with viral proteins. Due to technical advancements, three-dimensional interactions may now be visualized computationally utilizing molecular modeling and cryo-EM approaches. The uniqueness of viral domain repertoires, their evolution, and their activities during viral infection make viruses fascinating models for research. This chapter aims to provide readers a complete picture of the viral hijacking mechanism in protein-protein interactions.


Subject(s)
Host Microbial Interactions , Viral Proteins , Humans , Viral Proteins/chemistry
20.
Methods Mol Biol ; 2452: 197-212, 2022.
Article in English | MEDLINE | ID: covidwho-1844268

ABSTRACT

As the knowledge of biomolecules is increasing from the last decades, it is helping the researchers to understand the unsolved issues regarding virology. Recent technologies in high-throughput sequencing are providing the swift generation of SARS-CoV-2 genomic data with the basic inside of viral infection. Owing to various virus-host protein interactions, high-throughput technologies are unable to provide complete details of viral pathogenesis. Identifying the virus-host protein interactions using bioinformatics approaches can assist in understanding the mechanism of SARS-CoV-2 infection and pathogenesis. In this chapter, recent integrative bioinformatics approaches are discussed to help the virologists and computational biologists in the identification of structurally similar proteins of human and SARS-CoV-2 virus, and to predict the potential of virus-host interactions. Considering experimental and time limitations for effective viral drug development, computational aided drug design (CADD) can reduce the gap between drug prediction and development. More research with respect to evolutionary solutions could be helpful to make a new pipeline for virus-host protein-protein interactions and provide more understanding to disclose the cases of host switch, and also expand the virulence of the pathogen and host range in developing viral infections.


Subject(s)
COVID-19 , Computational Biology , Host Microbial Interactions , Host-Pathogen Interactions/genetics , Humans , Proteins , SARS-CoV-2/genetics
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