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  1. Article: Editorial: Endocrine organoids for modeling, drug development, and treatment of cancer and other diseases.

    Pidugu, Vijaya Kumar / Tharappel, Anil Mathew / Kumari, Sonam / Sanjiv, Kumar

    Frontiers in endocrinology

    2023  Volume 14, Page(s) 1292619

    MeSH term(s) Humans ; Neoplasms/drug therapy ; Organoids ; Drug Development
    Language English
    Publishing date 2023-09-25
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2592084-4
    ISSN 1664-2392
    ISSN 1664-2392
    DOI 10.3389/fendo.2023.1292619
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Inteins as Drug Targets and Therapeutic Tools.

    Tharappel, Anil Mathew / Li, Zhong / Li, Hongmin

    Frontiers in molecular biosciences

    2022  Volume 9, Page(s) 821146

    Abstract: Multidrug-resistant pathogens are of significant concern in recent years. Hence new antifungal and anti-bacterial drug targets are urgently needed before the situation goes beyond control. Inteins are polypeptides that self-splice from exteins without ... ...

    Abstract Multidrug-resistant pathogens are of significant concern in recent years. Hence new antifungal and anti-bacterial drug targets are urgently needed before the situation goes beyond control. Inteins are polypeptides that self-splice from exteins without the need for cofactors or external energy, resulting in joining of extein fragments. Inteins are present in many organisms, including human pathogens such as
    Language English
    Publishing date 2022-02-08
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2814330-9
    ISSN 2296-889X
    ISSN 2296-889X
    DOI 10.3389/fmolb.2022.821146
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Inteins as Drug Targets and Therapeutic Tools

    Anil Mathew Tharappel / Zhong Li / Hongmin Li

    Frontiers in Molecular Biosciences, Vol

    2022  Volume 9

    Abstract: Multidrug-resistant pathogens are of significant concern in recent years. Hence new antifungal and anti-bacterial drug targets are urgently needed before the situation goes beyond control. Inteins are polypeptides that self-splice from exteins without ... ...

    Abstract Multidrug-resistant pathogens are of significant concern in recent years. Hence new antifungal and anti-bacterial drug targets are urgently needed before the situation goes beyond control. Inteins are polypeptides that self-splice from exteins without the need for cofactors or external energy, resulting in joining of extein fragments. Inteins are present in many organisms, including human pathogens such as Mycobacterium tuberculosis, Cryptococcus neoformans, C. gattii, and Aspergillus fumigatus. Because intein elements are not present in human genes, they are attractive drug targets to develop antifungals and antibiotics. Thus far, a few inhibitors of intein splicing have been reported. Metal-ions such as Zn2+ and Cu2+, and platinum-containing compound cisplatin inhibit intein splicing in M. tuberculosis and C. neoformans by binding to the active site cysteines. A small-molecule inhibitor 6G-318S and its derivative 6G-319S are found to inhibit intein splicing in C. neoformans and C. gattii with a MIC in nanomolar concentrations. Inteins have also been used in many other applications. Intein can be used in activating a protein inside a cell using small molecules. Moreover, split intein can be used to deliver large genes in experimental gene therapy and to kill selected species in a mixed population of microbes by taking advantage of the toxin-antitoxin system. Furthermore, split inteins are used in synthesizing cyclic peptides and in developing cell culture model to study infectious viruses including SARS-CoV-2 in the biosafety level (BSL) 2 facility. This mini-review discusses the recent research developments of inteins in drug discovery and therapeutic research.
    Keywords intein ; inhibitor ; drug target ; therapeutic tool ; anti-microbial ; Biology (General) ; QH301-705.5
    Subject code 572
    Language English
    Publishing date 2022-02-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Calcimycin Inhibits

    Tharappel, Anil Mathew / Li, Zhong / Zhu, Yan Chun / Wu, Xiangmeng / Chaturvedi, Sudha / Zhang, Qing-Yu / Li, Hongmin

    ACS infectious diseases

    2022  Volume 8, Issue 9, Page(s) 1851–1868

    Abstract: Drug resistance is a significant concern in the treatment of diseases, including cryptococcosis caused ... ...

    Abstract Drug resistance is a significant concern in the treatment of diseases, including cryptococcosis caused by
    MeSH term(s) Animals ; Antifungal Agents/metabolism ; Antifungal Agents/pharmacology ; Calcimycin/metabolism ; Calcimycin/pharmacology ; Cryptococcosis/drug therapy ; Cryptococcus neoformans ; Fungal Proteins/chemistry ; Humans ; Inteins ; Mice ; Sequence Alignment
    Chemical Substances Antifungal Agents ; Fungal Proteins ; Calcimycin (37H9VM9WZL)
    Language English
    Publishing date 2022-08-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ISSN 2373-8227
    ISSN (online) 2373-8227
    DOI 10.1021/acsinfecdis.2c00137
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Targeting Crucial Host Factors of SARS-CoV-2.

    Tharappel, Anil Mathew / Samrat, Subodh Kumar / Li, Zhong / Li, Hongmin

    ACS infectious diseases

    2020  Volume 6, Issue 11, Page(s) 2844–2865

    Abstract: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide since its first incidence in Wuhan, China, in December 2019. Although the case fatality rate of COVID-19 appears to be lower ...

    Abstract Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide since its first incidence in Wuhan, China, in December 2019. Although the case fatality rate of COVID-19 appears to be lower than that of SARS and Middle East respiratory syndrome (MERS), the higher transmissibility of SARS-CoV-2 has caused the total fatality to surpass other viral diseases, reaching more than 1 million globally as of October 6, 2020. The rate at which the disease is spreading calls for a therapy that is useful for treating a large population. Multiple intersecting viral and host factor targets involved in the life cycle of the virus are being explored. Because of the frequent mutations, many coronaviruses gain zoonotic potential, which is dependent on the presence of cell receptors and proteases, and therefore the targeting of the viral proteins has some drawbacks, as strain-specific drug resistance can occur. Moreover, the limited number of proteins in a virus makes the number of available targets small. Although SARS-CoV and SARS-CoV-2 share common mechanisms of entry and replication, there are substantial differences in viral proteins such as the spike (S) protein. In contrast, targeting cellular factors may result in a broader range of therapies, reducing the chances of developing drug resistance. In this Review, we discuss the role of primary host factors such as the cell receptor angiotensin-converting enzyme 2 (ACE2), cellular proteases of S protein priming, post-translational modifiers, kinases, inflammatory cells, and their pharmacological intervention in the infection of SARS-CoV-2 and related viruses.
    MeSH term(s) Animals ; Antiviral Agents/pharmacology ; Betacoronavirus/physiology ; COVID-19 ; Coronavirus Infections/virology ; Gene Expression Regulation/drug effects ; Gene Expression Regulation/immunology ; Humans ; Pandemics ; Pneumonia, Viral/virology ; Receptors, Cell Surface/physiology ; SARS-CoV-2
    Chemical Substances Antiviral Agents ; Receptors, Cell Surface
    Keywords covid19
    Language English
    Publishing date 2020-10-28
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ISSN 2373-8227
    ISSN (online) 2373-8227
    DOI 10.1021/acsinfecdis.0c00456
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Broad-Spectrum Small-Molecule Inhibitors Targeting the SAM-Binding Site of Flavivirus NS5 Methyltransferase.

    Samrat, Subodh Kumar / Bashir, Qamar / Huang, Yiding / Trieshmann, Carl William / Tharappel, Anil Mathew / Zhang, Ran / Chen, Ke / Zheng, Y Geoge / Li, Zhong / Li, Hongmin

    ACS infectious diseases

    2023  Volume 9, Issue 7, Page(s) 1319–1333

    Abstract: Flavivirus infections, such as those caused by dengue virus (DENV), West Nile virus (WNV), yellow fever virus (YFV), and Zika virus (ZIKV), pose a rising threat to global health. There are no FDA-approved drugs for flaviviruses, although a small number ... ...

    Abstract Flavivirus infections, such as those caused by dengue virus (DENV), West Nile virus (WNV), yellow fever virus (YFV), and Zika virus (ZIKV), pose a rising threat to global health. There are no FDA-approved drugs for flaviviruses, although a small number of flaviviruses have vaccines. For flaviviruses or unknown viruses that may appear in the future, it is particularly desirable to identify broad-spectrum inhibitors. The NS5 protein is regarded as one of the most promising flavivirus drug targets because it is conserved across flaviviruses. In this study, we used FL-NAH, a fluorescent analog of the methyl donor
    MeSH term(s) Humans ; Flavivirus ; Methyltransferases/metabolism ; Zika Virus Infection ; Zika Virus/genetics ; Binding Sites ; Flavivirus Infections
    Chemical Substances Methyltransferases (EC 2.1.1.-)
    Language English
    Publishing date 2023-06-22
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2373-8227
    ISSN (online) 2373-8227
    DOI 10.1021/acsinfecdis.2c00571
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Targeting Crucial Host Factors of SARS-CoV-2

    Tharappel, Anil Mathew / Samrat, Subodh Kumar / Li, Zhong / Li, Hongmin

    ACS Infectious Diseases ; ISSN 2373-8227 2373-8227

    2020  

    Keywords covid19
    Language English
    Publisher American Chemical Society (ACS)
    Publishing country us
    Document type Article ; Online
    DOI 10.1021/acsinfecdis.0c00456
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article: Targeting Crucial Host Factors of SARS-CoV-2

    Tharappel, Anil Mathew / Samrat, Subodh Kumar / Li, Zhong / Li, Hongmin

    ACS Infect Dis

    Abstract: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide since its first incidence in Wuhan, China, in December 2019. Although the case fatality rate of COVID-19 appears to be lower ...

    Abstract Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide since its first incidence in Wuhan, China, in December 2019. Although the case fatality rate of COVID-19 appears to be lower than that of SARS and Middle East respiratory syndrome (MERS), the higher transmissibility of SARS-CoV-2 has caused the total fatality to surpass other viral diseases, reaching more than 1 million globally as of October 6, 2020. The rate at which the disease is spreading calls for a therapy that is useful for treating a large population. Multiple intersecting viral and host factor targets involved in the life cycle of the virus are being explored. Because of the frequent mutations, many coronaviruses gain zoonotic potential, which is dependent on the presence of cell receptors and proteases, and therefore the targeting of the viral proteins has some drawbacks, as strain-specific drug resistance can occur. Moreover, the limited number of proteins in a virus makes the number of available targets small. Although SARS-CoV and SARS-CoV-2 share common mechanisms of entry and replication, there are substantial differences in viral proteins such as the spike (S) protein. In contrast, targeting cellular factors may result in a broader range of therapies, reducing the chances of developing drug resistance. In this Review, we discuss the role of primary host factors such as the cell receptor angiotensin-converting enzyme 2 (ACE2), cellular proteases of S protein priming, post-translational modifiers, kinases, inflammatory cells, and their pharmacological intervention in the infection of SARS-CoV-2 and related viruses.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #894368
    Database COVID19

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  9. Article ; Online: Small-molecule inhibitors for the Prp8 intein as antifungal agents.

    Li, Zhong / Tharappel, Anil Mathew / Xu, Jimin / Lang, Yuekun / Green, Cathleen M / Zhang, Jing / Lin, Qishan / Chaturvedi, Sudha / Zhou, Jia / Belfort, Marlene / Li, Hongmin

    Proceedings of the National Academy of Sciences of the United States of America

    2021  Volume 118, Issue 2

    Abstract: Self-splicing proteins, called inteins, are present in many human pathogens, including the emerging fungal ... ...

    Abstract Self-splicing proteins, called inteins, are present in many human pathogens, including the emerging fungal threats
    MeSH term(s) Antifungal Agents/pharmacology ; Cryptococcus neoformans/genetics ; Cryptococcus neoformans/metabolism ; Cryptococcus neoformans/pathogenicity ; Fungal Proteins/metabolism ; Humans ; Inteins/genetics ; Introns/genetics ; Protein Splicing/genetics ; Protein Splicing/physiology ; RNA Splicing/genetics ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism ; Sequence Alignment/methods
    Chemical Substances Antifungal Agents ; Fungal Proteins ; PRPF8 protein, human ; RNA-Binding Proteins
    Language English
    Publishing date 2021-01-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2008815118
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Emetine inhibits Zika and Ebola virus infections through two molecular mechanisms: inhibiting viral replication and decreasing viral entry.

    Yang, Shu / Xu, Miao / Lee, Emily M / Gorshkov, Kirill / Shiryaev, Sergey A / He, Shihua / Sun, Wei / Cheng, Yu-Shan / Hu, Xin / Tharappel, Anil Mathew / Lu, Billy / Pinto, Antonella / Farhy, Chen / Huang, Chun-Teng / Zhang, Zirui / Zhu, Wenjun / Wu, Yuying / Zhou, Yi / Song, Guang /
    Zhu, Heng / Shamim, Khalida / Martínez-Romero, Carles / García-Sastre, Adolfo / Preston, Richard A / Jayaweera, Dushyantha T / Huang, Ruili / Huang, Wenwei / Xia, Menghang / Simeonov, Anton / Ming, Guoli / Qiu, Xiangguo / Terskikh, Alexey V / Tang, Hengli / Song, Hongjun / Zheng, Wei

    Cell discovery

    2018  Volume 4, Page(s) 31

    Abstract: The re-emergence of Zika virus (ZIKV) and Ebola virus (EBOV) poses serious and continued threats to the global public health. Effective therapeutics for these maladies is an unmet need. Here, we show that emetine, an anti-protozoal agent, potently ... ...

    Abstract The re-emergence of Zika virus (ZIKV) and Ebola virus (EBOV) poses serious and continued threats to the global public health. Effective therapeutics for these maladies is an unmet need. Here, we show that emetine, an anti-protozoal agent, potently inhibits ZIKV and EBOV infection with a low nanomolar half maximal inhibitory concentration (IC
    Language English
    Publishing date 2018-06-05
    Publishing country England
    Document type Journal Article
    ISSN 2056-5968
    ISSN 2056-5968
    DOI 10.1038/s41421-018-0034-1
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