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  1. Article ; Online: Deciphering the human cellular interactors of alphavirus unique domain of chikungunya virus.

    Ghildiyal, Ritu / Gabrani, Reema

    Virus research

    2021  Volume 295, Page(s) 198288

    Abstract: The life-threatening re-emerged chikungunya virus (CHIKV) can cause an epidemic outbreak and still has no vaccine available so far. Alphavirus unique domain (AUD) of CHIKV nsP3 is a multifunctional domain that remains conserved among alphaviruses and is ... ...

    Abstract The life-threatening re-emerged chikungunya virus (CHIKV) can cause an epidemic outbreak and still has no vaccine available so far. Alphavirus unique domain (AUD) of CHIKV nsP3 is a multifunctional domain that remains conserved among alphaviruses and is critical for CHIKV replication. The understanding of AUD-host protein-protein interactions and their association with the cellular processes concerning CHIKV infection are not well studied. In the current study, the protein-protein interactions of AUD and its human host were elucidated by screening of universal human cDNA library using yeast two-hybrid system. The chosen interactions were further validated by GST pull-down assay, and their network mapping was analyzed. The study revealed that the identified interactors are linked with the vesicle trafficking and transcription corepressor activities. Further, the interfacial residues of interactions between viral and host proteins were predicted, which will further provide the new platform to develop novel antivirals.
    MeSH term(s) Alphavirus/genetics ; Chikungunya Fever ; Chikungunya virus/genetics ; Humans ; Two-Hybrid System Techniques ; Viral Nonstructural Proteins/genetics ; Virus Replication/genetics
    Chemical Substances Viral Nonstructural Proteins
    Language English
    Publishing date 2021-01-05
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 605780-9
    ISSN 1872-7492 ; 0168-1702
    ISSN (online) 1872-7492
    ISSN 0168-1702
    DOI 10.1016/j.virusres.2020.198288
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  2. Article: Computational approach to decipher cellular interactors and drug targets during co-infection of SARS-CoV-2, Dengue, and Chikungunya virus.

    Ghildiyal, Ritu / Gabrani, Reema

    Virusdisease

    2021  Volume 32, Issue 1, Page(s) 55–64

    Abstract: The world is reeling under severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, and it will be frightening if compounded by other co-existing infections. The co-occurrence of the Dengue virus (DENV) and Chikungunya virus (CHIKV) has ... ...

    Abstract The world is reeling under severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, and it will be frightening if compounded by other co-existing infections. The co-occurrence of the Dengue virus (DENV) and Chikungunya virus (CHIKV) has been into existence, but recently the co-infection of DENV and SARS-CoV-2 has been reported. Thus, the possibility of DENV, CHIKV, and SARS-CoV-2 co-infection could be predicted in the future with enhanced vulnerability. It is essential to elucidate the host interactors and the connected pathways to understand the biological insights. The in silico approach using Cytoscape was exploited to elucidate the common human proteins interacting with DENV, CHIKV, and SARS-CoV-2 during their probable co-infection. In total, 17 interacting host proteins were identified showing association with envelope, structural, non-structural, and accessory proteins. Investigating the functional and biological behaviour using PANTHER, UniProtKB, and KEGG databases uncovered their association with several cellular pathways including, signaling pathways, RNA processing and transport, cell cycle, ubiquitination, and protein trafficking. Withal, exploring the DrugBank and Therapeutic Target Database, total seven druggable host proteins were predicted. Among all integrin beta-1, histone deacetylase-2 (HDAC2) and microtubule affinity-regulating kinase-3 were targeted by FDA approved molecules/ drugs. Furthermore, HDAC2 was predicted to be the most significant target, and some approved drugs are available against it. The predicted druggable targets and approved drugs could be investigated to obliterate the identified interactions that could assist in inhibiting viral infection.
    Language English
    Publishing date 2021-03-10
    Publishing country India
    Document type Journal Article
    ZDB-ID 2846993-8
    ISSN 2347-3517 ; 2347-3584
    ISSN (online) 2347-3517
    ISSN 2347-3584
    DOI 10.1007/s13337-021-00665-8
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  3. Article ; Online: Computational analysis of human host binding partners of chikungunya and dengue viruses during coinfection.

    Ghildiyal, Ritu / Gabrani, Reema

    Pathogens and disease

    2021  Volume 79, Issue 8

    Abstract: Mosquito-borne viral diseases like chikungunya and dengue infections can cause severe illness and have become major public health concerns. Chikungunya virus (CHIKV) and dengue virus (DENV) infections share similar primary clinical manifestations and are ...

    Abstract Mosquito-borne viral diseases like chikungunya and dengue infections can cause severe illness and have become major public health concerns. Chikungunya virus (CHIKV) and dengue virus (DENV) infections share similar primary clinical manifestations and are transmitted by the same vector. Thus, the probability of their coinfection gets increased with more severe clinical complications in the patients. The present study was undertaken to elucidate the common human interacting partners of CHIKV and DENV proteins during coinfection. The viral-host protein-protein interactome was constructed using Cytoscape. Subsequently, significant host interactors were identified during coinfection. The network analysis elucidated 57 human proteins interacting with both CHIKV and DENV, represented as hub-bottlenecks. The functional and biological analyses of the 40 hub-bottlenecks revealed that they are associated with phosphoinositide 3-kinases (PI3K)/AKT, p53 signaling pathways, regulation of cell cycle and apoptosis during coinfection. Moreover, the molecular docking analysis uncovered the tight and robust binding of selected hub-bottlenecks with CHIKV/DENV proteins. Additionally, 23 hub-bottlenecks were predicted as druggable candidates that could be targeted to eradicate the host-viral interactions. The elucidated common host binding partners during DENV and CHIKV coinfection as well as indicated approved drugs can support the therapeutics development.
    MeSH term(s) Animals ; Carrier Proteins ; Chikungunya Fever/metabolism ; Chikungunya Fever/virology ; Chikungunya virus/physiology ; Computational Biology/methods ; Dengue/metabolism ; Dengue/virology ; Dengue Virus/physiology ; Drug Discovery/methods ; Host-Pathogen Interactions ; Humans ; Models, Molecular ; Protein Binding ; Structure-Activity Relationship
    Chemical Substances Carrier Proteins
    Language English
    Publishing date 2021-09-22
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2049-632X
    ISSN (online) 2049-632X
    DOI 10.1093/femspd/ftab046
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Antiviral therapeutics for chikungunya virus.

    Ghildiyal, Ritu / Gabrani, Reema

    Expert opinion on therapeutic patents

    2020  Volume 30, Issue 6, Page(s) 467–480

    Abstract: ... ...

    Abstract Introduction
    MeSH term(s) Animals ; Antiviral Agents/administration & dosage ; Antiviral Agents/adverse effects ; Antiviral Agents/pharmacology ; Chikungunya Fever/drug therapy ; Chikungunya Fever/virology ; Chikungunya virus/drug effects ; Drug Development ; Drug Resistance, Viral ; Humans ; Patents as Topic ; Viral Vaccines/administration & dosage ; Virus Replication/drug effects
    Chemical Substances Antiviral Agents ; Viral Vaccines
    Keywords covid19
    Language English
    Publishing date 2020-04-17
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1186201-4
    ISSN 1744-7674 ; 0962-2594 ; 1354-3776
    ISSN (online) 1744-7674
    ISSN 0962-2594 ; 1354-3776
    DOI 10.1080/13543776.2020.1751817
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3962: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  5. Article: Computational approach to decipher cellular interactors and drug targets during co-infection of SARS-CoV-2, Dengue, and Chikungunya virus

    Ghildiyal, Ritu / Gabrani, Reema

    Virusdisease. 2021 Mar., v. 32, no. 1

    2021  

    Abstract: The world is reeling under severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, and it will be frightening if compounded by other co-existing infections. The co-occurrence of the Dengue virus (DENV) and Chikungunya virus (CHIKV) has ... ...

    Abstract The world is reeling under severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, and it will be frightening if compounded by other co-existing infections. The co-occurrence of the Dengue virus (DENV) and Chikungunya virus (CHIKV) has been into existence, but recently the co-infection of DENV and SARS-CoV-2 has been reported. Thus, the possibility of DENV, CHIKV, and SARS-CoV-2 co-infection could be predicted in the future with enhanced vulnerability. It is essential to elucidate the host interactors and the connected pathways to understand the biological insights. The in silico approach using Cytoscape was exploited to elucidate the common human proteins interacting with DENV, CHIKV, and SARS-CoV-2 during their probable co-infection. In total, 17 interacting host proteins were identified showing association with envelope, structural, non-structural, and accessory proteins. Investigating the functional and biological behaviour using PANTHER, UniProtKB, and KEGG databases uncovered their association with several cellular pathways including, signaling pathways, RNA processing and transport, cell cycle, ubiquitination, and protein trafficking. Withal, exploring the DrugBank and Therapeutic Target Database, total seven druggable host proteins were predicted. Among all integrin beta-1, histone deacetylase-2 (HDAC2) and microtubule affinity-regulating kinase-3 were targeted by FDA approved molecules/ drugs. Furthermore, HDAC2 was predicted to be the most significant target, and some approved drugs are available against it. The predicted druggable targets and approved drugs could be investigated to obliterate the identified interactions that could assist in inhibiting viral infection.
    Keywords Chikungunya virus ; Dengue virus ; RNA ; Severe acute respiratory syndrome coronavirus 2 ; cell cycle ; computer simulation ; databases ; dengue ; drugs ; histones ; humans ; integrins ; microtubules ; mixed infection ; pandemic ; therapeutics ; ubiquitination
    Language English
    Dates of publication 2021-03
    Size p. 55-64.
    Publishing place Springer India
    Document type Article
    Note NAL-AP-2-clean
    ZDB-ID 2846993-8
    ISSN 2347-3517 ; 2347-3584
    ISSN (online) 2347-3517
    ISSN 2347-3584
    DOI 10.1007/s13337-021-00665-8
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  6. Article: In silico study of chikungunya polymerase, a potential target for inhibitors.

    Ghildiyal, Ritu / Gupta, Sanjay / Gabrani, Reema / Joshi, Gopal / Gupta, Amita / Chaudhary, V K / Gupta, Vandana

    Virusdisease

    2019  Volume 30, Issue 3, Page(s) 394–402

    Abstract: Non-structural protein 4 (nsP4) polymerase of chikungunya virus (CHIKV) has a crucial role in genome replication and hence could act as a promising target for novel therapeutics. Though, nsP4 is important in viral life cycle, but it is less explored as ... ...

    Abstract Non-structural protein 4 (nsP4) polymerase of chikungunya virus (CHIKV) has a crucial role in genome replication and hence could act as a promising target for novel therapeutics. Though, nsP4 is important in viral life cycle, but it is less explored as therapeutic target. The catalytic core of nsP4 Polymerase includes conserved GDD motif which is present not only across different CHIKV strains but also across other
    Language English
    Publishing date 2019-10-26
    Publishing country India
    Document type Journal Article
    ZDB-ID 2846993-8
    ISSN 2347-3517 ; 2347-3584
    ISSN (online) 2347-3517
    ISSN 2347-3584
    DOI 10.1007/s13337-019-00547-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: In silico study of chikungunya polymerase, a potential target for inhibitors

    Ghildiyal, Ritu / Gupta, Sanjay / Gabrani, Reema / Joshi, Gopal / Gupta, Amita / Chaudhary, V. K / Gupta, Vandana

    Virusdisease. 2019 Sept., v. 30, no. 3

    2019  

    Abstract: Non-structural protein 4 (nsP4) polymerase of chikungunya virus (CHIKV) has a crucial role in genome replication and hence could act as a promising target for novel therapeutics. Though, nsP4 is important in viral life cycle, but it is less explored as ... ...

    Abstract Non-structural protein 4 (nsP4) polymerase of chikungunya virus (CHIKV) has a crucial role in genome replication and hence could act as a promising target for novel therapeutics. Though, nsP4 is important in viral life cycle, but it is less explored as therapeutic target. The catalytic core of nsP4 Polymerase includes conserved GDD motif which is present not only across different CHIKV strains but also across other Alphaviruses. This emphasizes the uniqueness and importance of this motif in the functioning of nsP4 polymerase and hence, we focused on GDD motif for docking of drug molecules. Herein, a model of nsP4 polymerase was developed using Swiss Model, validated by Ramachandran plot and molecular dynamic simulation. Molecular docking was performed using LeadIT FlexX flexible docking module with FDA approved drug molecule library. On the basis of flexX score, top 5 leads with flexX scores − 33.7588, − 30.2555, − 29.6043, − 28.916 and − 28.5042 were selected. The bonding pattern of these leads were analysed in discovery studio and were further screened on the basis of molecular dynamic simulation studies. Simulation analysis revealed that only the top lead, Mitoxantrone Hydrochloride which is an anticancer drug and is currently indicated in leukemias and lymphomas interacted favourably and stably with nsP4. Our findings suggest that Mitoxantrone Hydrochloride can be a potential novel inhibitor of CHIKV polymerase and should be further validated by in vitro assays.
    Keywords antineoplastic agents ; in vitro studies ; lead ; lymphoma ; simulation models
    Language English
    Dates of publication 2019-09
    Size p. 394-402.
    Publishing place Springer India
    Document type Article
    ZDB-ID 2846993-8
    ISSN 2347-3517 ; 2347-3584
    ISSN (online) 2347-3517
    ISSN 2347-3584
    DOI 10.1007/s13337-019-00547-0
    Database NAL-Catalogue (AGRICOLA)

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  8. Article: Phytochemicals as Antiviral Agents: Recent Updates

    Ghildiyal, Ritu / Prakash, Vijeta / Chaudhary, V. K. / Gupta, Vandana / Gabrani, Reema

    Plant-derived Bioactives: Production, Properties and Therapeutic Applications

    Abstract: The epidemic of viral diseases is a global concern, mandating an urgent need of most promising antivirals Some of the viral diseases can be cured by approved antiviral drugs, but for others still do not have any vaccines or drugs available Most of the ... ...

    Abstract The epidemic of viral diseases is a global concern, mandating an urgent need of most promising antivirals Some of the viral diseases can be cured by approved antiviral drugs, but for others still do not have any vaccines or drugs available Most of the approved antiviral drugs are somehow directly or indirectly associated with side effects, which eventually raise the need for the development of antivirals based on natural phytochemicals Globally, the development of antivirals is shifting towards the plant-derived products as they are less toxic and has less chance to develop resistance Phytochemicals have been exploited traditionally for the cure of many diseases, and also have been reported to inhibit viral replication/transcription Most of them inhibit the viruses either during the viral entry inside the host cell or during their replication Moreover, 50% of the drugs derived from plants are being used in the Western nations Plants have a variety of phytochemicals like flavonoids, terpenoids, lignins, alkaloids, and coumarins that are having antioxidant activity, and help to inhibit viral genome Various plant-derived products have been well studied against viruses like herpes virus, human immunodeficiency virus (HIV), influenza, and hepatitis virus More recently, Coronavirus disease (COVID-19) caused by a newly identified coronavirus has become pandemic, and affected world’s population severely However, there are still less explored phytochemicals for the inhibition of viruses like dengue virus, chikungunya virus, and other alphaviruses In this chapter, we will emphasize on the reported phytochemicals and their derivatives, having antiviral properties and their mechanism to treat viral diseases
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #825436
    Database COVID19

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