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  1. Article ; Online: Broad spectrum post-entry inhibitors of coronavirus replication: Cardiotonic steroids and monensin.

    Jahanshahi, Shahrzad / Ouyang, Hong / Ahmed, Choudhary / Zahedi Amiri, Ali / Dahal, Subha / Mao, Yu-Qian / Van Ommen, David A J / Malty, Ramy / Duan, Wenming / Been, Terek / Hernandez, Javier / Mangos, Maria / Nurtanto, Jocelyn / Babu, Mohan / Attisano, Liliana / Houry, Walid A / Moraes, Theo J / Cochrane, Alan

    Virology

    2023  Volume 589, Page(s) 109915

    Abstract: A small molecule screen identified several cardiotonic steroids (digitoxin and ouabain) and the ionophore monensin as potent inhibitors of HCoV-229E, HCoV-OC43, and SARS-CoV-2 replication with ... ...

    Abstract A small molecule screen identified several cardiotonic steroids (digitoxin and ouabain) and the ionophore monensin as potent inhibitors of HCoV-229E, HCoV-OC43, and SARS-CoV-2 replication with EC
    MeSH term(s) Humans ; Cardiac Glycosides/pharmacology ; Monensin/pharmacology ; Ouabain/pharmacology ; Coronavirus 229E, Human ; Digitoxin/pharmacology ; Antiviral Agents/pharmacology
    Chemical Substances Cardiac Glycosides ; Monensin (906O0YJ6ZP) ; Ouabain (5ACL011P69) ; Digitoxin (E90NZP2L9U) ; Antiviral Agents
    Language English
    Publishing date 2023-10-31
    Publishing country United States
    Document type Journal Article
    ZDB-ID 200425-2
    ISSN 1096-0341 ; 0042-6822
    ISSN (online) 1096-0341
    ISSN 0042-6822
    DOI 10.1016/j.virol.2023.109915
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  2. Article ; Online: On a path toward a broad-spectrum anti-viral: inhibition of HIV-1 and coronavirus replication by SR kinase inhibitor harmine.

    Dahal, Subha / Clayton, Kiera / Cabral, Tyler / Cheng, Ran / Jahanshahi, Shahrzad / Ahmed, Choudhary / Koirala, Amrit / Villasmil Ocando, Alonso / Malty, Ramy / Been, Terek / Hernandez, Javier / Mangos, Maria / Shen, David / Babu, Mohan / Calarco, John / Chabot, Benoit / Attisano, Liliana / Houry, Walid A / Cochrane, Alan

    Journal of virology

    2023  Volume 97, Issue 10, Page(s) e0039623

    Abstract: Importance: This study highlights the crucial role RNA processing plays in regulating viral gene expression and replication. By targeting SR kinases, we identified harmine as a potent inhibitor of HIV-1 as well as coronavirus (HCoV-229E and multiple ... ...

    Abstract Importance: This study highlights the crucial role RNA processing plays in regulating viral gene expression and replication. By targeting SR kinases, we identified harmine as a potent inhibitor of HIV-1 as well as coronavirus (HCoV-229E and multiple SARS-CoV-2 variants) replication. Harmine inhibits HIV-1 protein expression and reduces accumulation of HIV-1 RNAs in both cell lines and primary CD4
    MeSH term(s) Humans ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Coronavirus/drug effects ; Coronavirus/physiology ; Coronavirus Infections/drug therapy ; Harmine/pharmacology ; Harmine/therapeutic use ; HIV-1/drug effects ; HIV-1/physiology ; Virus Replication/drug effects
    Chemical Substances Antiviral Agents ; Harmine (4FHH5G48T7)
    Language English
    Publishing date 2023-09-14
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80174-4
    ISSN 1098-5514 ; 0022-538X
    ISSN (online) 1098-5514
    ISSN 0022-538X
    DOI 10.1128/jvi.00396-23
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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    ab Jg. 2022: Lesesaal (EG)

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  3. Article ; Online: WFhb1-1 plays an important role in resistance against Fusarium head blight in wheat.

    Paudel, Bimal / Zhuang, Yongbin / Galla, Aravind / Dahal, Subha / Qiu, Yinjie / Ma, Anjun / Raihan, Tajbir / Yen, Yang

    Scientific reports

    2020  Volume 10, Issue 1, Page(s) 7794

    Abstract: Fusarium head blight (FHB) is a severe disease of wheat (Triticum aestivum L.). Qfhb1 is the most important quantitative trait locus (QTL) for FHB resistance. We previously identified wheat gene WFhb1-1 (aka WFhb1-c1) as a candidate for FHB resistance ... ...

    Abstract Fusarium head blight (FHB) is a severe disease of wheat (Triticum aestivum L.). Qfhb1 is the most important quantitative trait locus (QTL) for FHB resistance. We previously identified wheat gene WFhb1-1 (aka WFhb1-c1) as a candidate for FHB resistance gene. Here we report that WFhb1-1 has been cloned. The gene (GenBank # KU304333.1) consists of a single exon, encoding a putative membrane protein of 127 amino acids. WFhb1-1 protein produced in Pichia pastoris inhibits growth of both F. graminearum and P. pastoris in culture. Western Blotting with anti- WFhb1-1 antibody revealed a significant decrease (p < 0.01) in WFhb1-1 accumulation, 12 hours post Fusarium inoculation in non-Qfhb1-carrier wheat but not in Qfhb1-carrier wheat. Overexpressing WFhb1-1 in non-Qfhb1-carrier wheat led to a significant decrease (p < 0.01) in Fusarium-damaged rachis rate, Fusarium-diseased kernel rate and DON content in harvested kernels, while silencing WFhb1-1 in Qfhb1-carrier wheat resulted in a significant increase (p < 0.01) in FHB severity. Therefore, WFhb1-1 is an important FHB resistance gene with a potential antifungal function and probably a key functional component of Qfhb1 in wheat. A model regarding how WFhb1-1 functions in FHB resistance/susceptibility is hypothesized and discussed.
    MeSH term(s) Amino Acid Substitution ; Base Sequence ; Chromosome Mapping ; Cloning, Molecular ; Disease Resistance/genetics ; Fusarium ; Gene Expression Profiling ; Gene Expression Regulation, Plant ; Genes, Plant ; Mutation ; Plant Diseases/genetics ; Plant Diseases/microbiology ; Plants, Genetically Modified ; Quantitative Trait Loci ; Quantitative Trait, Heritable ; Sequence Analysis, DNA ; Triticum/genetics ; Triticum/microbiology
    Language English
    Publishing date 2020-05-08
    Publishing country England
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-020-64777-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The Genetics and Genome-Wide Screening of Regrowth Loci, a Key Component of Perennialism in

    Ma, Anjun / Qiu, Yinjie / Raihan, Tajbir / Paudel, Bimal / Dahal, Subha / Zhuang, Yongbin / Galla, Aravind / Auger, Donald / Yen, Yang

    G3 (Bethesda, Md.)

    2019  Volume 9, Issue 5, Page(s) 1393–1403

    Abstract: Perennialism is common among the higher plants, yet little is known about its inheritance. Previous genetic studies of the perennialism ... ...

    Abstract Perennialism is common among the higher plants, yet little is known about its inheritance. Previous genetic studies of the perennialism in
    MeSH term(s) Chromosome Mapping ; Crosses, Genetic ; Genetic Association Studies ; Genetic Testing ; Genome, Plant ; Genome-Wide Association Study ; Genomics/methods ; Phenotype ; Plant Development/genetics ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; Zea mays/genetics
    Language English
    Publishing date 2019-05-07
    Publishing country England
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2629978-1
    ISSN 2160-1836 ; 2160-1836
    ISSN (online) 2160-1836
    ISSN 2160-1836
    DOI 10.1534/g3.118.200977
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: WFhb1-1 plays an important role in resistance against Fusarium head blight in wheat

    Bimal Paudel / Yongbin Zhuang / Aravind Galla / Subha Dahal / Yinjie Qiu / Anjun Ma / Tajbir Raihan / Yang Yen

    Scientific Reports, Vol 10, Iss 1, Pp 1-

    2020  Volume 15

    Abstract: Abstract Fusarium head blight (FHB) is a severe disease of wheat (Triticum aestivum L.). Qfhb1 is the most important quantitative trait locus (QTL) for FHB resistance. We previously identified wheat gene WFhb1-1 (aka WFhb1-c1) as a candidate for FHB ... ...

    Abstract Abstract Fusarium head blight (FHB) is a severe disease of wheat (Triticum aestivum L.). Qfhb1 is the most important quantitative trait locus (QTL) for FHB resistance. We previously identified wheat gene WFhb1-1 (aka WFhb1-c1) as a candidate for FHB resistance gene. Here we report that WFhb1-1 has been cloned. The gene (GenBank # KU304333.1) consists of a single exon, encoding a putative membrane protein of 127 amino acids. WFhb1-1 protein produced in Pichia pastoris inhibits growth of both F. graminearum and P. pastoris in culture. Western Blotting with anti- WFhb1-1 antibody revealed a significant decrease (p < 0.01) in WFhb1-1 accumulation, 12 hours post Fusarium inoculation in non-Qfhb1-carrier wheat but not in Qfhb1-carrier wheat. Overexpressing WFhb1-1 in non-Qfhb1-carrier wheat led to a significant decrease (p < 0.01) in Fusarium-damaged rachis rate, Fusarium-diseased kernel rate and DON content in harvested kernels, while silencing WFhb1-1 in Qfhb1-carrier wheat resulted in a significant increase (p < 0.01) in FHB severity. Therefore, WFhb1-1 is an important FHB resistance gene with a potential antifungal function and probably a key functional component of Qfhb1 in wheat. A model regarding how WFhb1-1 functions in FHB resistance/susceptibility is hypothesized and discussed.
    Keywords Medicine ; R ; Science ; Q
    Subject code 571
    Language English
    Publishing date 2020-05-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Opposing roles of CLK SR kinases in controlling HIV-1 gene expression and latency.

    Dahal, Subha / Clayton, Kiera / Been, Terek / Fernet-Brochu, Raphaële / Ocando, Alonso Villasmil / Balachandran, Ahalya / Poirier, Mikaël / Maldonado, Rebecca Kaddis / Shkreta, Lulzim / Boligan, Kayluz Frias / Guvenc, Furkan / Rahman, Fariha / Branch, Donald / Bell, Brendan / Chabot, Benoit / Gray-Owen, Scott D / Parent, Leslie J / Cochrane, Alan

    Retrovirology

    2022  Volume 19, Issue 1, Page(s) 18

    Abstract: Background: The generation of over 69 spliced HIV-1 mRNAs from one primary transcript by alternative RNA splicing emphasizes the central role that RNA processing plays in HIV-1 replication. Control is mediated in part through the action of host SR ... ...

    Abstract Background: The generation of over 69 spliced HIV-1 mRNAs from one primary transcript by alternative RNA splicing emphasizes the central role that RNA processing plays in HIV-1 replication. Control is mediated in part through the action of host SR proteins whose activity is regulated by multiple SR kinases (CLK1-4, SRPKs).
    Methods: Both shRNA depletion and small molecule inhibitors of host SR kinases were used in T cell lines and primary cells to evaluate the role of these factors in the regulation of HIV-1 gene expression. Effects on virus expression were assessed using western blotting, RT-qPCR, and immunofluorescence.
    Results: The studies demonstrate that SR kinases play distinct roles; depletion of CLK1 enhanced HIV-1 gene expression, reduction of CLK2 or SRPK1 suppressed it, whereas CLK3 depletion had a modest impact. The opposing effects of CLK1 vs. CLK2 depletion were due to action at distinct steps; reduction of CLK1 increased HIV-1 promoter activity while depletion of CLK2 affected steps after transcript initiation. Reduced CLK1 expression also enhanced the response to several latency reversing agents, in part, by increasing the frequency of responding cells, consistent with a role in regulating provirus latency. To determine whether small molecule modulation of SR kinase function could be used to control HIV-1 replication, we screened a GSK library of protein kinase inhibitors (PKIS) and identified several pyrazolo[1,5-b] pyridazine derivatives that suppress HIV-1 gene expression/replication with an EC
    Conclusions: These findings demonstrate the unique roles played by individual SR kinases in regulating HIV-1 gene expression, validating the targeting of these functions to either enhance latency reversal, essential for "Kick-and-Kill" strategies, or to silence HIV protein expression for "Block-and-Lock" strategies.
    MeSH term(s) Alternative Splicing ; Gene Expression ; HIV-1/physiology ; Protein Kinase Inhibitors/pharmacology ; RNA, Viral/genetics ; Virus Latency
    Chemical Substances Protein Kinase Inhibitors ; RNA, Viral
    Language English
    Publishing date 2022-08-19
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2142602-8
    ISSN 1742-4690 ; 1742-4690
    ISSN (online) 1742-4690
    ISSN 1742-4690
    DOI 10.1186/s12977-022-00605-4
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  7. Article ; Online: The Thiazole-5-Carboxamide GPS491 Inhibits HIV-1, Adenovirus, and Coronavirus Replication by Altering RNA Processing/Accumulation.

    Dahal, Subha / Cheng, Ran / Cheung, Peter K / Been, Terek / Malty, Ramy / Geng, Melissa / Manianis, Sarah / Shkreta, Lulzim / Jahanshahi, Shahrazad / Toutant, Johanne / Chan, Rose / Park, Sean / Brockman, Mark A / Babu, Mohan / Mubareka, Samira / Mossman, Karen / Banerjee, Arinjay / Gray-Owen, Scott / Brown, Martha /
    Houry, Walid A / Chabot, Benoit / Grierson, David / Cochrane, Alan

    Viruses

    2021  Volume 14, Issue 1

    Abstract: Medicinal chemistry optimization of a previously described stilbene inhibitor of HIV-1, 5350150 (2-(2-(5-nitro-2-thienyl)vinyl)quinoline), led to the identification of the thiazole-5-carboxamide derivative (GPS491), which retained potent anti-HIV-1 ... ...

    Abstract Medicinal chemistry optimization of a previously described stilbene inhibitor of HIV-1, 5350150 (2-(2-(5-nitro-2-thienyl)vinyl)quinoline), led to the identification of the thiazole-5-carboxamide derivative (GPS491), which retained potent anti-HIV-1 activity with reduced toxicity. In this report, we demonstrate that the block of HIV-1 replication by GPS491 is accompanied by a drastic inhibition of viral gene expression (IC
    MeSH term(s) Adenoviridae/drug effects ; Adenoviridae/physiology ; Antiviral Agents/chemistry ; Antiviral Agents/pharmacology ; Cell Line ; Coronavirus/classification ; Coronavirus/drug effects ; Coronavirus/physiology ; Gene Expression/drug effects ; HIV-1/drug effects ; HIV-1/physiology ; Humans ; RNA Processing, Post-Transcriptional/drug effects ; RNA Splicing Factors/metabolism ; RNA, Viral/metabolism ; Thiazoles/chemistry ; Thiazoles/pharmacology ; Virus Replication/drug effects
    Chemical Substances Antiviral Agents ; RNA Splicing Factors ; RNA, Viral ; Thiazoles
    Language English
    Publishing date 2021-12-30
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v14010060
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  8. Article: The Thiazole-5-Carboxamide GPS491 Inhibits HIV-1, Adenovirus, and Coronavirus Replication by Altering RNA Processing/Accumulation

    Dahal, Subha / Cheng, Ran / Cheung, Peter K. / Been, Terek / Malty, Ramy / Geng, Melissa / Manianis, Sarah / Shkreta, Lulzim / Jahanshahi, Shahrazad / Toutant, Johanne / Chan, Rose / Park, Sean / Brockman, Mark A. / Babu, Mohan / Mubareka, Samira / Mossman, Karen / Banerjee, Arinjay / Gray-Owen, Scott / Brown, Martha /
    Houry, Walid A. / Chabot, Benoit / Grierson, David / Cochrane, Alan

    Viruses. 2021 Dec. 30, v. 14, no. 1

    2021  

    Abstract: Medicinal chemistry optimization of a previously described stilbene inhibitor of HIV-1, 5350150 (2-(2-(5-nitro-2-thienyl)vinyl)quinoline), led to the identification of the thiazole-5-carboxamide derivative (GPS491), which retained potent anti-HIV-1 ... ...

    Abstract Medicinal chemistry optimization of a previously described stilbene inhibitor of HIV-1, 5350150 (2-(2-(5-nitro-2-thienyl)vinyl)quinoline), led to the identification of the thiazole-5-carboxamide derivative (GPS491), which retained potent anti-HIV-1 activity with reduced toxicity. In this report, we demonstrate that the block of HIV-1 replication by GPS491 is accompanied by a drastic inhibition of viral gene expression (IC₅₀ ~ 0.25 µM), and alterations in the production of unspliced, singly spliced, and multiply spliced HIV-1 RNAs. GPS491 also inhibited the replication of adenovirus and multiple coronaviruses. Low µM doses of GPS491 reduced adenovirus infectious yield ~1000 fold, altered virus early gene expression/viral E1A RNA processing, blocked viral DNA amplification, and inhibited late (hexon) gene expression. Loss of replication of multiple coronaviruses (229E, OC43, SARS-CoV2) upon GPS491 addition was associated with the inhibition of viral structural protein expression and the formation of virus particles. Consistent with the observed changes in viral RNA processing, GPS491 treatment induced selective alterations in the accumulation/phosphorylation/function of splicing regulatory SR proteins. Our study establishes that a compound that impacts the activity of cellular factors involved in RNA processing can prevent the replication of several viruses with minimal effect on cell viability.
    Keywords Adenoviridae ; DNA ; Orthocoronavirinae ; RNA ; cell viability ; gene expression ; phosphorylation ; protein synthesis ; quinoline ; stilbenes ; structural proteins ; toxicity ; viruses
    Language English
    Dates of publication 2021-1230
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    ZDB-ID 2516098-9
    ISSN 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v14010060
    Database NAL-Catalogue (AGRICOLA)

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