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1.
J Mol Biol ; 434(6): 167277, 2022 03 30.
Article in English | MEDLINE | ID: covidwho-1851576

ABSTRACT

Establishment of the interferon (IFN)-mediated antiviral state provides a crucial initial line of defense against viral infection. Numerous genes that contribute to this antiviral state remain to be identified. Using a loss-of-function strategy, we screened an original library of 1156 siRNAs targeting 386 individual curated human genes in stimulated microglial cells infected with Zika virus (ZIKV), an emerging RNA virus that belongs to the flavivirus genus. The screen recovered twenty-one potential host proteins that modulate ZIKV replication in an IFN-dependent manner, including the previously known IFITM3 and LY6E. Further characterization contributed to delineate the spectrum of action of these genes towards other pathogenic RNA viruses, including Hepatitis C virus and SARS-CoV-2. Our data revealed that APOL3 acts as a proviral factor for ZIKV and several other related and unrelated RNA viruses. In addition, we showed that MTA2, a chromatin remodeling factor, possesses potent flavivirus-specific antiviral functions induced by IFN. Our work identified previously unrecognized genes that modulate the replication of RNA viruses in an IFN-dependent manner, opening new perspectives to target weakness points in the life cycle of these viruses.


Subject(s)
COVID-19 , Flavivirus , Zika Virus Infection , Zika Virus , Antiviral Agents/pharmacology , Flavivirus/genetics , Histone Deacetylases , Humans , Interferons/genetics , Membrane Proteins , RNA-Binding Proteins , Repressor Proteins , SARS-CoV-2 , Virus Replication/genetics , Zika Virus/genetics , Zika Virus Infection/genetics
2.
Nat Commun ; 13(1): 1722, 2022 03 31.
Article in English | MEDLINE | ID: covidwho-1773975

ABSTRACT

The rapidly growing popularity of RNA structure probing methods is leading to increasingly large amounts of available RNA structure information. This demands the development of efficient tools for the identification of RNAs sharing regions of structural similarity by direct comparison of their reactivity profiles, hence enabling the discovery of conserved structural features. We here introduce SHAPEwarp, a largely sequence-agnostic SHAPE-guided algorithm for the identification of structurally-similar regions in RNA molecules. Analysis of Dengue, Zika and coronavirus genomes recapitulates known regulatory RNA structures and identifies novel highly-conserved structural elements. This work represents a preliminary step towards the model-free search and identification of shared and conserved RNA structural features within transcriptomes.


Subject(s)
Zika Virus Infection , Zika Virus , Algorithms , Humans , Nucleic Acid Conformation , RNA/chemistry , RNA/genetics , RNA, Guide , Sequence Analysis, RNA/methods , Zika Virus/genetics
3.
Genome Res ; 32(5): 956-967, 2022 05.
Article in English | MEDLINE | ID: covidwho-1764740

ABSTRACT

RNA homodimerization is important for various physiological processes, including the assembly of membraneless organelles, RNA subcellular localization, and packaging of viral genomes. However, understanding RNA dimerization has been hampered by the lack of systematic in vivo detection methods. Here, we show that CLASH, PARIS, and other RNA proximity ligation methods detect RNA homodimers transcriptome-wide as "overlapping" chimeric reads that contain more than one copy of the same sequence. Analyzing published proximity ligation data sets, we show that RNA:RNA homodimers mediated by direct base-pairing are rare across the human transcriptome, but highly enriched in specific transcripts, including U8 snoRNA, U2 snRNA, and a subset of tRNAs. Mutations in the homodimerization domain of U8 snoRNA impede dimerization in vitro and disrupt zebrafish development in vivo, suggesting an evolutionarily conserved role of this domain. Analysis of virus-infected cells reveals homodimerization of SARS-CoV-2 and Zika genomes, mediated by specific palindromic sequences located within protein-coding regions of N gene in SARS-CoV-2 and NS2A gene in Zika. We speculate that regions of viral genomes involved in homodimerization may constitute effective targets for antiviral therapies.


Subject(s)
COVID-19 , Zika Virus Infection , Zika Virus , Animals , Base Sequence , RNA, Small Nucleolar/genetics , RNA, Viral/genetics , SARS-CoV-2/genetics , Zebrafish/genetics , Zika Virus/genetics , Zika Virus Infection/genetics
4.
Cell Rep ; 38(10): 110434, 2022 03 08.
Article in English | MEDLINE | ID: covidwho-1729611

ABSTRACT

Type I interferons (IFN-I) are essential to establish antiviral innate immunity. Unanchored (or free) polyubiquitin (poly-Ub) has been shown to regulate IFN-I responses. However, few unanchored poly-Ub interactors are known. To identify factors regulated by unanchored poly-Ub in a physiological setting, we developed an approach to isolate unanchored poly-Ub from lung tissue. We identified the RNA helicase DHX16 as a potential pattern recognition receptor (PRR). Silencing of DHX16 in cells and in vivo diminished IFN-I responses against influenza virus. These effects extended to members of other virus families, including Zika and SARS-CoV-2. DHX16-dependent IFN-I production requires RIG-I and unanchored K48-poly-Ub synthesized by the E3-Ub ligase TRIM6. DHX16 recognizes a signal in influenza RNA segments that undergo splicing and requires its RNA helicase motif for direct, high-affinity interactions with specific viral RNAs. Our study establishes DHX16 as a PRR that partners with RIG-I for optimal activation of antiviral immunity requiring unanchored poly-Ub.


Subject(s)
DEAD Box Protein 58 , Interferon Type I , RNA Helicases , RNA, Viral , Receptors, Immunologic , Zika Virus Infection , Zika Virus , COVID-19 , DEAD Box Protein 58/immunology , Humans , Immunity, Innate , Interferon Type I/immunology , RNA Helicases/immunology , Receptors, Immunologic/immunology , SARS-CoV-2 , Tripartite Motif Proteins , Zika Virus/genetics , Zika Virus Infection/immunology
5.
Nihon Yakurigaku Zasshi ; 157(2): 134-138, 2022.
Article in Japanese | MEDLINE | ID: covidwho-1714692

ABSTRACT

RNA viruses are responsible for several infectious diseases, including dengue fever, Zika fever, and COVID-19. Reverse genetics is a powerful tool to elucidate which domain or mutations in RNA viruses determine their pathogenicity and ability to evade antiviral drugs and host immune response. Previous reverse genetics systems for flaviviruses and coronaviruses have been technically challenging and time-consuming, thereby hampering the further understanding of events during viral evolution. A novel reverse genetics system-circular polymerase extension reaction (CPER)-has been developed to overcome this limitation. CPER is based on PCR-mediated assembly of DNA fragments that encode the whole genome of these viruses. CPER requires a relatively short time to introduce specific mutations into the viral genome of flaviviruses and SARS-CoV-2. In this review article, we explain the mode of action of this system and discuss the future direction of reverse genetics for RNA viruses.


Subject(s)
COVID-19 , Zika Virus Infection , Zika Virus , Genome, Viral , Humans , RNA, Viral/genetics , Reverse Genetics , SARS-CoV-2 , Zika Virus/genetics , Zika Virus Infection/genetics
6.
Am J Trop Med Hyg ; 106(3): 896-899, 2022 01 24.
Article in English | MEDLINE | ID: covidwho-1649221

ABSTRACT

We provide evidence of concurrent and close sequential infections between SARS-CoV-2 and select arboviruses-namely, chikungunya virus (CHIKV); dengue viruses 1, 2, and 3 (DENV1-3), and Zika virus (ZIKV)-in patients in Guerrero, southwest Mexico, in 2020-2021. The study population consisted of 176 febrile patients with laboratory evidence of SARS-CoV-2 infection. Sera from all patients were serologically and antigenically tested for seven arboviruses known to occur in Guerrero. Eighteen patients contained CHIKV IgM, six of whom also contained CHIKV RNA. Another 16 patients contained flavivirus antigen. The flaviviruses responsible for the infections were identified by plaque reduction neutralization test as DENV1 (two patients), DENV2 (five patients), DENV3 (three patients), ZIKV (three patients), and an undetermined flavivirus (three patients). In summary, we identified patients in Guerrero, Mexico, with concurrent or recent sequential infections between SARS-CoV-2 and select arboviruses, exemplifying the importance of performing differential diagnosis in regions where these viruses cocirculate.


Subject(s)
Arboviruses , COVID-19 , Chikungunya Fever , Coinfection , Dengue Virus , Dengue , Zika Virus Infection , Zika Virus , COVID-19/epidemiology , Dengue/diagnosis , Dengue Virus/genetics , Humans , Mexico/epidemiology , SARS-CoV-2 , Zika Virus/genetics , Zika Virus Infection/epidemiology
7.
Genomics ; 114(2): 110270, 2022 03.
Article in English | MEDLINE | ID: covidwho-1633861

ABSTRACT

Viruses can subvert a number of cellular processes including splicing in order to block innate antiviral responses, and many viruses interact with cellular splicing machinery. SARS-CoV-2 infection was shown to suppress global mRNA splicing, and at least 10 SARS-CoV-2 proteins bind specifically to one or more human RNAs. Here, we investigate 17 published experimental and clinical datasets related to SARS-CoV-2 infection, datasets from the betacoronaviruses SARS-CoV and MERS, as well as Streptococcus pneumonia, HCV, Zika virus, Dengue virus, influenza H3N2, and RSV. We show that genes showing differential alternative splicing in SARS-CoV-2 have a similar functional profile to those of SARS-CoV and MERS and affect a diverse set of genes and biological functions, including many closely related to virus biology. Additionally, the differentially spliced transcripts of cells infected by coronaviruses were more likely to undergo intron-retention, contain a pseudouridine modification, and have a smaller number of exons as compared with differentially spliced transcripts in the control groups. Viral load in clinical COVID-19 samples was correlated with isoform distribution of differentially spliced genes. A significantly higher number of ribosomal genes are affected by differential alternative splicing and gene expression in betacoronavirus samples, and the betacoronavirus differentially spliced genes are depleted for binding sites of RNA-binding proteins. Our results demonstrate characteristic patterns of differential splicing in cells infected by SARS-CoV-2, SARS-CoV, and MERS. The alternative splicing changes observed in betacoronaviruses infection potentially modify a broad range of cellular functions, via changes in the functions of the products of a diverse set of genes involved in different biological processes.


Subject(s)
COVID-19 , Influenza, Human , Zika Virus Infection , Zika Virus , Alternative Splicing , COVID-19/genetics , Humans , Influenza A Virus, H3N2 Subtype , SARS-CoV-2/genetics , Zika Virus/genetics
8.
Emerg Infect Dis ; 27(11): 2971-2973, 2021 11.
Article in English | MEDLINE | ID: covidwho-1559753

ABSTRACT

We reconstructed the 2016-2017 Zika virus epidemic in Puerto Rico by using complete genomes to uncover the epidemic's origin, spread, and evolutionary dynamics. Our study revealed that the epidemic was propelled by multiple introductions that spread across the island, intricate evolutionary patterns, and ≈10 months of cryptic transmission.


Subject(s)
Epidemics , Zika Virus Infection , Zika Virus , Evolution, Molecular , Humans , Puerto Rico/epidemiology , Zika Virus/genetics , Zika Virus Infection/epidemiology
9.
FEBS Lett ; 595(23): 2854-2871, 2021 12.
Article in English | MEDLINE | ID: covidwho-1508599

ABSTRACT

SARS-CoV-2 has infected hundreds of millions of people with over four million dead, resulting in one of the worst global pandemics in recent history. Neurological symptoms associated with COVID-19 include anosmia, ageusia, headaches, confusion, delirium, and strokes. These may manifest due to viral entry into the central nervous system (CNS) through the blood-brain barrier (BBB) by means of ill-defined mechanisms. Here, we summarize the abilities of SARS-CoV-2 and other neurotropic RNA viruses, including Zika virus and Nipah virus, to cross the BBB into the CNS, highlighting the role of magnetic resonance imaging (MRI) in assessing presence and severity of brain structural changes in COVID-19 patients. We present new insight into key mutations in SARS-CoV-2 variants B.1.1.7 (P681H) and B.1.617.2 (P681R), which may impact on neuropilin 1 (NRP1) binding and CNS invasion. We postulate that SARS-CoV-2 may infect both peripheral cells capable of crossing the BBB and brain endothelial cells to traverse the BBB and spread into the brain. COVID-19 patients can be followed up with MRI modalities to better understand the long-term effects of COVID-19 on the brain.


Subject(s)
Blood-Brain Barrier , Henipavirus Infections , Nipah Virus , SARS-CoV-2 , Zika Virus Infection , Zika Virus , Blood-Brain Barrier/metabolism , Blood-Brain Barrier/physiopathology , Blood-Brain Barrier/virology , COVID-19/epidemiology , COVID-19/genetics , COVID-19/metabolism , COVID-19/physiopathology , Henipavirus Infections/epidemiology , Henipavirus Infections/genetics , Henipavirus Infections/metabolism , Henipavirus Infections/physiopathology , Humans , Mutation , Nipah Virus/genetics , Nipah Virus/metabolism , SARS-CoV-2/genetics , SARS-CoV-2/metabolism , Zika Virus/genetics , Zika Virus/metabolism , Zika Virus Infection/epidemiology , Zika Virus Infection/genetics , Zika Virus Infection/metabolism , Zika Virus Infection/physiopathology
10.
FEBS Lett ; 595(23): 2854-2871, 2021 12.
Article in English | MEDLINE | ID: covidwho-1508598

ABSTRACT

SARS-CoV-2 has infected hundreds of millions of people with over four million dead, resulting in one of the worst global pandemics in recent history. Neurological symptoms associated with COVID-19 include anosmia, ageusia, headaches, confusion, delirium, and strokes. These may manifest due to viral entry into the central nervous system (CNS) through the blood-brain barrier (BBB) by means of ill-defined mechanisms. Here, we summarize the abilities of SARS-CoV-2 and other neurotropic RNA viruses, including Zika virus and Nipah virus, to cross the BBB into the CNS, highlighting the role of magnetic resonance imaging (MRI) in assessing presence and severity of brain structural changes in COVID-19 patients. We present new insight into key mutations in SARS-CoV-2 variants B.1.1.7 (P681H) and B.1.617.2 (P681R), which may impact on neuropilin 1 (NRP1) binding and CNS invasion. We postulate that SARS-CoV-2 may infect both peripheral cells capable of crossing the BBB and brain endothelial cells to traverse the BBB and spread into the brain. COVID-19 patients can be followed up with MRI modalities to better understand the long-term effects of COVID-19 on the brain.


Subject(s)
Blood-Brain Barrier , Henipavirus Infections , Nipah Virus , SARS-CoV-2 , Zika Virus Infection , Zika Virus , Blood-Brain Barrier/metabolism , Blood-Brain Barrier/physiopathology , Blood-Brain Barrier/virology , COVID-19/epidemiology , COVID-19/genetics , COVID-19/metabolism , COVID-19/physiopathology , Henipavirus Infections/epidemiology , Henipavirus Infections/genetics , Henipavirus Infections/metabolism , Henipavirus Infections/physiopathology , Humans , Mutation , Nipah Virus/genetics , Nipah Virus/metabolism , SARS-CoV-2/genetics , SARS-CoV-2/metabolism , Zika Virus/genetics , Zika Virus/metabolism , Zika Virus Infection/epidemiology , Zika Virus Infection/genetics , Zika Virus Infection/metabolism , Zika Virus Infection/physiopathology
11.
Viruses ; 13(11)2021 10 26.
Article in English | MEDLINE | ID: covidwho-1488755

ABSTRACT

Understanding the dynamic relationship between viral pathogens and cellular host factors is critical to furthering our knowledge of viral replication, disease mechanisms and development of anti-viral therapeutics. CRISPR genome editing technology has enhanced this understanding, by allowing identification of pro-viral and anti-viral cellular host factors for a wide range of viruses, most recently the cause of the COVID-19 pandemic, SARS-CoV-2. This review will discuss how CRISPR knockout and CRISPR activation genome-wide screening methods are a robust tool to investigate the viral life cycle and how other class 2 CRISPR systems are being repurposed for diagnostics.


Subject(s)
CRISPR-Cas Systems , Communicable Diseases, Emerging/virology , Coronavirus Infections/virology , Coronavirus/genetics , Gene Editing , Zika Virus Infection/virology , Zika Virus/genetics , COVID-19/diagnosis , COVID-19/virology , Clustered Regularly Interspaced Short Palindromic Repeats , Communicable Diseases, Emerging/diagnosis , Coronavirus/physiology , Coronavirus Infections/diagnosis , Host-Pathogen Interactions , Humans , SARS-CoV-2/genetics , Zika Virus/physiology , Zika Virus Infection/diagnosis
12.
J Virol ; 95(24): e0059621, 2021 11 23.
Article in English | MEDLINE | ID: covidwho-1443352

ABSTRACT

Cellular factors have important roles in all facets of the flavivirus replication cycle. Deciphering viral-host protein interactions is essential for understanding the flavivirus life cycle as well as development of effective antiviral strategies. To uncover novel host factors that are co-opted by multiple flaviviruses, a CRISPR/Cas9 genome wide knockout (KO) screen was employed to identify genes required for replication of Zika virus (ZIKV). Receptor for Activated Protein C Kinase 1 (RACK1) was identified as a novel host factor required for ZIKV replication, which was confirmed via complementary experiments. Depletion of RACK1 via siRNA demonstrated that RACK1 is important for replication of a wide range of mosquito- and tick-borne flaviviruses, including West Nile Virus (WNV), Dengue Virus (DENV), Powassan Virus (POWV) and Langat Virus (LGTV) as well as the coronavirus SARS-CoV-2, but not for YFV, EBOV, VSV or HSV. Notably, flavivirus replication was only abrogated when RACK1 expression was dampened prior to infection. Utilising a non-replicative flavivirus model, we show altered morphology of viral replication factories and reduced formation of vesicle packets (VPs) in cells lacking RACK1 expression. In addition, RACK1 interacted with NS1 protein from multiple flaviviruses; a key protein for replication complex formation. Overall, these findings reveal RACK1's crucial role to the biogenesis of pan-flavivirus replication organelles. IMPORTANCE Cellular factors are critical in all facets of viral lifecycles, where overlapping interactions between the virus and host can be exploited as possible avenues for the development of antiviral therapeutics. Using a genome-wide CRISPR knockout screening approach to identify novel cellular factors important for flavivirus replication we identified RACK1 as a pro-viral host factor for both mosquito- and tick-borne flaviviruses in addition to SARS-CoV-2. Using an innovative flavivirus protein expression system, we demonstrate for the first time the impact of the loss of RACK1 on the formation of viral replication factories known as 'vesicle packets' (VPs). In addition, we show that RACK1 can interact with numerous flavivirus NS1 proteins as a potential mechanism by which VP formation can be induced by the former.


Subject(s)
CRISPR-Cas Systems , Flavivirus/genetics , Neoplasm Proteins/genetics , Receptors for Activated C Kinase/genetics , Virus Replication , A549 Cells , Aedes , Animals , COVID-19 , Chlorocebus aethiops , Culicidae , Dengue Virus/genetics , Genome-Wide Association Study , HEK293 Cells , Host-Pathogen Interactions/genetics , Humans , RNA, Small Interfering/metabolism , RNA, Viral/metabolism , SARS-CoV-2 , Vero Cells , West Nile virus/genetics , Zika Virus/genetics , Zika Virus Infection/virology
13.
J Mol Biol ; 434(6): 167277, 2022 03 30.
Article in English | MEDLINE | ID: covidwho-1440208

ABSTRACT

Establishment of the interferon (IFN)-mediated antiviral state provides a crucial initial line of defense against viral infection. Numerous genes that contribute to this antiviral state remain to be identified. Using a loss-of-function strategy, we screened an original library of 1156 siRNAs targeting 386 individual curated human genes in stimulated microglial cells infected with Zika virus (ZIKV), an emerging RNA virus that belongs to the flavivirus genus. The screen recovered twenty-one potential host proteins that modulate ZIKV replication in an IFN-dependent manner, including the previously known IFITM3 and LY6E. Further characterization contributed to delineate the spectrum of action of these genes towards other pathogenic RNA viruses, including Hepatitis C virus and SARS-CoV-2. Our data revealed that APOL3 acts as a proviral factor for ZIKV and several other related and unrelated RNA viruses. In addition, we showed that MTA2, a chromatin remodeling factor, possesses potent flavivirus-specific antiviral functions induced by IFN. Our work identified previously unrecognized genes that modulate the replication of RNA viruses in an IFN-dependent manner, opening new perspectives to target weakness points in the life cycle of these viruses.


Subject(s)
COVID-19 , Flavivirus , Zika Virus Infection , Zika Virus , Antiviral Agents/pharmacology , Flavivirus/genetics , Histone Deacetylases , Humans , Interferons/genetics , Membrane Proteins , RNA-Binding Proteins , Repressor Proteins , SARS-CoV-2 , Virus Replication/genetics , Zika Virus/genetics , Zika Virus Infection/genetics
14.
Cell Host Microbe ; 29(9): 1333-1335, 2021 09 08.
Article in English | MEDLINE | ID: covidwho-1401314

ABSTRACT

SARS-CoV-2 has mutually illuminated our collective knowledge and knowledge gaps, particularly in antiviral defense and therapeutic strategies. A recent study in Science (Poirier et al., 2021) uncovers an ancient antiviral mechanism that mammals utilize to suppress viruses, including SARS-CoV-2 and Zika virus, that could have broad implications for therapeutic strategies.


Subject(s)
Argonaute Proteins/metabolism , COVID-19/prevention & control , Interferons/immunology , RNA Interference/physiology , Ribonuclease III/metabolism , Zika Virus Infection/prevention & control , Animals , Cell Line , HEK293 Cells , Humans , RNA, Small Interfering/genetics , RNA, Viral/metabolism , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Virus Replication , Zika Virus/genetics , Zika Virus/immunology
15.
Nat Commun ; 11(1): 3749, 2020 07 27.
Article in English | MEDLINE | ID: covidwho-1376193

ABSTRACT

xrRNAs from flaviviruses survive in host cells because of their exceptional dichotomic response to the unfolding action of different enzymes. They can be unwound, and hence copied, by replicases, and yet can resist degradation by exonucleases. How the same stretch of xrRNA can encode such diverse responses is an open question. Here, by using atomistic models and translocation simulations, we uncover an elaborate and directional mechanism for how stress propagates when the two xrRNA ends, [Formula: see text] and [Formula: see text], are driven through a pore. Pulling the [Formula: see text] end, as done by replicases, elicits a progressive unfolding; pulling the [Formula: see text] end, as done by exonucleases, triggers a counterintuitive molecular tightening. Thus, in what appears to be a remarkable instance of intra-molecular tensegrity, the very pulling of the [Formula: see text] end is what boosts resistance to translocation and consequently to degradation. The uncovered mechanistic principle might be co-opted to design molecular meta-materials.


Subject(s)
RNA, Viral/metabolism , Zika Virus/genetics , Base Sequence , Nucleic Acid Conformation , RNA Transport , RNA, Viral/chemistry , RNA, Viral/genetics , Stress, Mechanical , Thermodynamics
16.
Science ; 373(6551): 231-236, 2021 07 09.
Article in English | MEDLINE | ID: covidwho-1304152

ABSTRACT

In mammals, early resistance to viruses relies on interferons, which protect differentiated cells but not stem cells from viral replication. Many other organisms rely instead on RNA interference (RNAi) mediated by a specialized Dicer protein that cleaves viral double-stranded RNA. Whether RNAi also contributes to mammalian antiviral immunity remains controversial. We identified an isoform of Dicer, named antiviral Dicer (aviD), that protects tissue stem cells from RNA viruses-including Zika virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-by dicing viral double-stranded RNA to orchestrate antiviral RNAi. Our work sheds light on the molecular regulation of antiviral RNAi in mammalian innate immunity, in which different cell-intrinsic antiviral pathways can be tailored to the differentiation status of cells.


Subject(s)
DEAD-box RNA Helicases/genetics , DEAD-box RNA Helicases/metabolism , RNA Interference , RNA Viruses/physiology , RNA, Viral/metabolism , Ribonuclease III/genetics , Ribonuclease III/metabolism , Stem Cells/enzymology , Stem Cells/virology , Alternative Splicing , Animals , Brain/enzymology , Brain/virology , Cell Line , DEAD-box RNA Helicases/chemistry , Humans , Immunity, Innate , Isoenzymes/chemistry , Isoenzymes/genetics , Isoenzymes/metabolism , Mice , Organoids/enzymology , Organoids/virology , RNA Virus Infections/enzymology , RNA Virus Infections/immunology , RNA Virus Infections/virology , RNA Viruses/genetics , RNA Viruses/immunology , RNA, Double-Stranded/metabolism , RNA, Small Interfering/metabolism , Ribonuclease III/chemistry , SARS-CoV-2/genetics , SARS-CoV-2/immunology , SARS-CoV-2/physiology , Virus Replication , Zika Virus/genetics , Zika Virus/immunology , Zika Virus/physiology , Zika Virus Infection/enzymology , Zika Virus Infection/immunology , Zika Virus Infection/virology
17.
Trop Doct ; 51(4): 606-607, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1261234

ABSTRACT

As international travels and destinations increase, travel-related infections increase. It is reported that 6-87% of the travellers contract travel-related infection during or after the trip. Vector-associated pathogens comprise a significant percentage of travel-related infections. Apart from the ubiquitous COVID19, threats such as Dengue, Chikungunya and Zika virus and tick-borne agents have emerged or re-emerged in recent years. The fact that these infections are carried with similar vectors and cause similar symptoms makes diagnosis difficult. Herein, a case of travel-associated infection with nonspecific symptoms is presented.


Subject(s)
COVID-19 , Chikungunya Fever , Dengue , Malaria , Zika Virus Infection , Zika Virus , Chikungunya Fever/diagnosis , Dengue/diagnosis , Humans , Malaria/diagnosis , SARS-CoV-2 , Travel , Travel-Related Illness , Zika Virus/genetics , Zika Virus Infection/diagnosis
18.
Comb Chem High Throughput Screen ; 25(3): 414-428, 2022.
Article in English | MEDLINE | ID: covidwho-1256209

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection has become a worldwide pandemic and created an utmost crisis across the globe. To mitigate the crisis, the design of vaccine is the crucial solution. The frequent mutation of the virus demands generalized vaccine candidates, which would be effective for all mutated strains at present and for the strains that would evolve due to further new mutations in the virus. OBJECTIVE: The objective of this study is to identify more frequently occurring mutated variants of SARS-CoV-2 and to suggest peptide vaccine candidates effective against the viral strains considered. METHODS: In this study, we have identified all currently prevailing mutated strains of SARS-CoV-2 through 2D Polar plot and Quotient Radius characterization descriptor. Then, by considering the top eight mutation strains, which are significant due to their frequency of occurrence, peptide regions suitable for vaccine design have been identified with the help of a mathematical model, 2D Polygon Representation, followed by the evaluation of epitope potential, ensuring that there is no case of any autoimmune threat. Lastly, in order to verify whether this entire approach is applicable for vaccine design against any other virus in general, we have made a comparative study between the peptide vaccine candidates prescribed for the Zika virus using the current approach and a list of potential vaccine candidates for the same already established in the past. RESULTS: We have finally suggested three generalized peptide regions which would be suitable as sustainable peptide vaccine candidates against SARS-CoV-2 irrespective of its currently prevailing strains as well any other variant of the same that may appear in the future. We also observed that during the comparative study using the case of E protein of Zika virus, the peptide regions suggested using the new approach that matches with the already established results. CONCLUSION: The study, therefore, illustrates an approach that would help in developing peptide vaccine against SARS-CoV-2 by suggesting those peptide regions which can be targeted irrespective of any mutated form of this virus. The consistency with which this entire approach was also able to figure out similar vaccine candidates for Zika virus with utmost accuracy proves that this protocol can be extended for peptide vaccine design against any other viruses in the future.


Subject(s)
COVID-19 , Vaccines , Zika Virus Infection , Zika Virus , COVID-19 Vaccines , Humans , Peptides , SARS-CoV-2 , Zika Virus/genetics
19.
Cells ; 10(3)2021 03 02.
Article in English | MEDLINE | ID: covidwho-1125490

ABSTRACT

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


Subject(s)
Coronavirus Nucleocapsid Proteins/metabolism , DEAD Box Protein 58/metabolism , Interferons/metabolism , Receptors, Immunologic/metabolism , SARS-CoV-2/metabolism , DEAD Box Protein 58/genetics , Host-Pathogen Interactions/genetics , Humans , Interferon Regulatory Factor-3/genetics , Interferon Regulatory Factor-3/metabolism , Interferon Type I/genetics , Interferon Type I/metabolism , Interferon-gamma/genetics , Interferon-gamma/metabolism , Interferons/genetics , Orthomyxoviridae/genetics , Orthomyxoviridae/metabolism , Phosphoproteins/metabolism , Poly C/pharmacology , Poly I/pharmacology , Promoter Regions, Genetic , /metabolism , Receptors, Immunologic/genetics , SARS-CoV-2/genetics , Signal Transduction/drug effects , Signal Transduction/genetics , Transcription Factors/metabolism , Tripartite Motif Proteins/metabolism , Ubiquitin-Protein Ligases/metabolism , Up-Regulation , Zika Virus/genetics , Zika Virus/metabolism
20.
Comput Biol Med ; 131: 104247, 2021 04.
Article in English | MEDLINE | ID: covidwho-1056506

ABSTRACT

A non-standard bioinformatics method, 4D-Dynamic Representation of DNA/RNA Sequences, aiming at an analysis of the information available in nucleotide databases, has been formulated. The sequences are represented by sets of "material points" in a 4D space - 4D-dynamic graphs. The graphs representing the sequences are treated as "rigid bodies" and characterized by values analogous to the ones used in the classical dynamics. As the graphical representations of the sequences, the projections of the graphs into 2D and 3D spaces are used. The method has been applied to an analysis of the complete genome sequences of the 2019 novel coronavirus. As a result, 2D and 3D classification maps are obtained. The coordinate axes in the maps correspond to the values derived from the exact formulas characterizing the graphs: the coordinates of the centers of mass and the 4D moments of inertia. The points in the maps represent sequences and their coordinates are used as the classifiers. The main result of this work has been derived from the 3D classification maps. The distribution of clusters of points which emerged in these maps, supports the hypothesis that SARS-CoV-2 may have originated in bat and in pangolin. Pilot calculations for Zika virus sequence data prove that the proposed approach is also applicable to a description of time evolution of genome sequences of viruses.


Subject(s)
Algorithms , Base Sequence , COVID-19/genetics , Computational Biology , Genome, Viral , SARS-CoV-2/genetics , Animals , Chiroptera/virology , Humans , Pangolins/virology , Phylogeny , Zika Virus/genetics , Zika Virus Infection/genetics
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