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  1. Article: CNP blocks mitochondrial depolarization and inhibits SARS-CoV-2 replication

    Logue, James / Melville, Victoria M / Ardanuy, Jeremy / Frieman, Matthew B

    bioRxiv : the preprint server for biology

    2023  

    Abstract: The COVID-19 pandemic has claimed over 6.5 million lives worldwide and continues to have lasting impacts on the world's healthcare and economic systems. Several approved and emergency authorized therapeutics that inhibit early stages of the virus ... ...

    Abstract The COVID-19 pandemic has claimed over 6.5 million lives worldwide and continues to have lasting impacts on the world's healthcare and economic systems. Several approved and emergency authorized therapeutics that inhibit early stages of the virus replication cycle have been developed however, effective late-stage therapeutical targets have yet to be identified. To that end, our lab identified that 2',3' cyclic-nucleotide 3'-phosphodiesterase (CNP) inhibits SARS-CoV-2 virion assembly. We show that CNP inhibits the generation of new SARS-CoV-2 virions, reducing intracellular titers without inhibiting viral structural protein translation. Additionally, we show that targeting of CNP to mitochondria is necessary for inhibition, blocking mitochondrial depolarization and implicating CNP's proposed role as an inhibitor of the mitochondrial permeabilization transition pore (mPTP) as the mechanism of virion assembly inhibition. We also demonstrate that an adenovirus expressing virus expressing both human ACE2 and CNP inhibits SARS-CoV-2 titers to undetectable levels in lungs of mice. Collectively, this work shows the potential of CNP to be a new SARS-CoV-2 antiviral target.
    Language English
    Publishing date 2023-12-19
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.06.09.544327
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: CNP blocks mitochondrial depolarization and inhibits SARS-CoV-2 replication in vitro and in vivo.

    Logue, James / Melville, Victoria M / Ardanuy, Jeremy / Frieman, Matthew B

    PLoS pathogens

    2023  Volume 19, Issue 12, Page(s) e1011870

    Abstract: The COVID-19 pandemic has claimed over 6.5 million lives worldwide and continues to have lasting impacts on the world's healthcare and economic systems. Several approved and emergency authorized therapeutics that inhibit early stages of the virus ... ...

    Abstract The COVID-19 pandemic has claimed over 6.5 million lives worldwide and continues to have lasting impacts on the world's healthcare and economic systems. Several approved and emergency authorized therapeutics that inhibit early stages of the virus replication cycle have been developed however, effective late-stage therapeutical targets have yet to be identified. To that end, our lab identified that 2',3' cyclic-nucleotide 3'-phosphodiesterase (CNP) inhibits SARS-CoV-2 virion assembly. We show that CNP inhibits the generation of new SARS-CoV-2 virions, reducing intracellular titers without inhibiting viral structural protein translation. Additionally, we show that targeting of CNP to mitochondria is necessary for inhibition, blocking mitochondrial depolarization and implicating CNP's proposed role as an inhibitor of the mitochondrial permeabilization transition pore (mPTP) as the mechanism of virion assembly inhibition. We also demonstrate that an adenovirus expressing virus expressing both human ACE2 and CNP inhibits SARS-CoV-2 titers to undetectable levels in lungs of mice. Collectively, this work shows the potential of CNP to be a new SARS-CoV-2 antiviral target.
    MeSH term(s) Mice ; Humans ; Animals ; SARS-CoV-2 ; COVID-19/metabolism ; Pandemics ; Mitochondria/metabolism ; Virus Assembly ; Antiviral Agents/metabolism
    Chemical Substances Antiviral Agents
    Language English
    Publishing date 2023-12-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7374
    ISSN (online) 1553-7374
    ISSN 1553-7374
    DOI 10.1371/journal.ppat.1011870
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: COVID-19: Knowns, Unknowns, and Questions.

    Weston, Stuart / Frieman, Matthew B

    mSphere

    2020  Volume 5, Issue 2

    Abstract: The recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the Hubei province in China in late 2019 demonstrates the epidemic potential of coronaviruses. The rapid spread of this virus across the world in only 2 months ... ...

    Abstract The recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the Hubei province in China in late 2019 demonstrates the epidemic potential of coronaviruses. The rapid spread of this virus across the world in only 2 months highlights the transmissibility of this family of viruses and the significant morbidity and mortality that they can cause. We highlight the current state of knowledge of coronavirus biology while answering questions concerning the current outbreak of SARS-CoV-2.
    MeSH term(s) Betacoronavirus ; COVID-19 ; China/epidemiology ; Coronavirus Infections/epidemiology ; Coronavirus Infections/transmission ; Humans ; Pandemics ; Pneumonia, Viral/epidemiology ; Pneumonia, Viral/transmission ; Risk Factors ; SARS-CoV-2
    Keywords covid19
    Language English
    Publishing date 2020-03-18
    Publishing country United States
    Document type Journal Article
    ISSN 2379-5042
    ISSN (online) 2379-5042
    DOI 10.1128/mSphere.00203-20
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The continued epidemic threat of SARS-CoV-2 and implications for the future of global public health.

    Sheahan, Timothy P / Frieman, Matthew B

    Current opinion in virology

    2020  Volume 40, Page(s) 37–40

    Abstract: A new coronavirus (CoV) called SARS-CoV-2 emerged in Wuhan, China in December 2019 as the etiological agent of a viral pneumonia called COVID-19. The global spread of SARS-CoV-2 has been so extensive that the WHO declared COVID-19 a pandemic on March 11, ...

    Abstract A new coronavirus (CoV) called SARS-CoV-2 emerged in Wuhan, China in December 2019 as the etiological agent of a viral pneumonia called COVID-19. The global spread of SARS-CoV-2 has been so extensive that the WHO declared COVID-19 a pandemic on March 11, 2020. Below, we discuss the emergence of SARS-CoV-2 and provide the historical context, which strongly suggests emerging CoVs provide an immediate threat to global public health and will continue to do so in the future.
    MeSH term(s) Animals ; Betacoronavirus ; COVID-19 ; China/epidemiology ; Communicable Diseases, Emerging/epidemiology ; Communicable Diseases, Emerging/virology ; Coronavirus Infections/epidemiology ; Disease Reservoirs/virology ; Global Health ; Humans ; Pandemics ; Pneumonia, Viral/epidemiology ; SARS-CoV-2 ; World Health Organization
    Keywords covid19
    Language English
    Publishing date 2020-06-04
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2611378-8
    ISSN 1879-6265 ; 1879-6257
    ISSN (online) 1879-6265
    ISSN 1879-6257
    DOI 10.1016/j.coviro.2020.05.010
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Placental SARS-CoV-2 infection and its implications for increased risk of adverse pregnancy outcomes.

    Wang, Bingbing / Shen, Wei-Bin / Townsel, Courtney / Baracco, Lauren / Logue, James / Reece, E Albert / Frieman, Matthew B / Yang, Peixin

    American journal of perinatology

    2024  

    Abstract: Introduction: Pregnant women are at increased risk of COVID-19. This could be explained through the prism of physiologic and immunologic changes in pregnancy. In addition, certain immunological reactions originate in the placenta in response to viral ... ...

    Abstract Introduction: Pregnant women are at increased risk of COVID-19. This could be explained through the prism of physiologic and immunologic changes in pregnancy. In addition, certain immunological reactions originate in the placenta in response to viral infections.
    Objective: This study aimed to investigate whether SARS-CoV-2 can infect the human placenta and discuss its implications in the pathogenesis of adverse pregnancy outcomes.
    Study design: We conducted a retrospective cohort study in which we collected placental specimens from pregnant women who had a laboratory-confirmed SARS-CoV-2 infection. We performed RNA in situ hybridization (RNA-ISH) assay on formalin-fixed paraffin-embedded (FFPE) tissues to establish the in vivo evidence for placental infectivity by this corona virus. In addition, we infected trophoblast isolated from uninfected term human placenta with SARS-CoV-2 variants to further provide in vitro evidence for such an infectivity.
    Results: There was a total of 21 cases enrolled, which included five cases of spontaneous preterm birth (SPTB) and two intrauterine fetal demises (IUFDs). Positive staining of positive-sense strand (PSS) of SARS-CoV-2 virions was detected in 15 placentas including four SPTB and both IUFDs. In vitro infection assay demonstrated that SARS-CoV-2 virions were highly capable of infecting both cytotrophoblast and syncytiotrophoblast.
    Conclusion: This study implies that placental SARS-CoV-2 infection may be associated with an increased risk of adverse obstetrical outcomes.
    Language English
    Publishing date 2024-05-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 605671-4
    ISSN 1098-8785 ; 0735-1631
    ISSN (online) 1098-8785
    ISSN 0735-1631
    DOI 10.1055/a-2323-0854
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: The continued epidemic threat of SARS-CoV-2 and implications for the future of global public health

    Sheahan, Timothy P / Frieman, Matthew B

    Curr Opin Virol

    Abstract: A new coronavirus (CoV) called SARS-CoV-2 emerged in Wuhan, China in December 2019 as the etiological agent of a viral pneumonia called COVID-19. The global spread of SARS-CoV-2 has been so extensive that the WHO declared COVID-19 a pandemic on March 11, ...

    Abstract A new coronavirus (CoV) called SARS-CoV-2 emerged in Wuhan, China in December 2019 as the etiological agent of a viral pneumonia called COVID-19. The global spread of SARS-CoV-2 has been so extensive that the WHO declared COVID-19 a pandemic on March 11, 2020. Below, we discuss the emergence of SARS-CoV-2 and provide the historical context, which strongly suggests emerging CoVs provide an immediate threat to global public health and will continue to do so in the future.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #526854
    Database COVID19

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  7. Article: COVID-19: Knowns, Unknowns, and Questions

    Weston, Stuart / Frieman, Matthew B

    MSphere

    Abstract: The recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the Hubei province in China in late 2019 demonstrates the epidemic potential of coronaviruses. The rapid spread of this virus across the world in only 2 months ... ...

    Abstract The recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the Hubei province in China in late 2019 demonstrates the epidemic potential of coronaviruses. The rapid spread of this virus across the world in only 2 months highlights the transmissibility of this family of viruses and the significant morbidity and mortality that they can cause. We highlight the current state of knowledge of coronavirus biology while answering questions concerning the current outbreak of SARS-CoV-2.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #9910
    Database COVID19

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  8. Article ; Online: The continued epidemic threat of SARS-CoV-2 and implications for the future of global public health

    Sheahan, Timothy P. / Frieman, Matthew B.

    Current Opinion in Virology

    2020  

    Abstract: A new coronavirus (CoV) called SARS-CoV-2 emerged in Wuhan, China in December 2019 as the etiological agent of a viral pneumonia called COVID-19. The global spread of SARS-CoV-2 has been so extensive that the WHO declared COVID-19 a pandemic on March 11, ...

    Abstract A new coronavirus (CoV) called SARS-CoV-2 emerged in Wuhan, China in December 2019 as the etiological agent of a viral pneumonia called COVID-19. The global spread of SARS-CoV-2 has been so extensive that the WHO declared COVID-19 a pandemic on March 11, 2020. Below, we discuss the emergence of SARS-CoV-2 and provide the historical context, which strongly suggests emerging CoVs provide an immediate threat to global public health and will continue to do so in the future.
    Keywords covid19
    Language English
    Publishing country us
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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  9. Article ; Online: COVID-19

    Weston, Stuart / Frieman, Matthew B.

    mSphere

    Knowns, Unknowns, and Questions

    2020  Volume 5, Issue 2

    Abstract: ABSTRACT The recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the Hubei province in China in late 2019 demonstrates the epidemic potential of coronaviruses. The rapid spread of this virus across the world in only 2 ... ...

    Abstract ABSTRACT The recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the Hubei province in China in late 2019 demonstrates the epidemic potential of coronaviruses. The rapid spread of this virus across the world in only 2 months highlights the transmissibility of this family of viruses and the significant morbidity and mortality that they can cause. We highlight the current state of knowledge of coronavirus biology while answering questions concerning the current outbreak of SARS-CoV-2.
    Keywords covid19
    Language English
    Publisher American Society for Microbiology
    Publishing country us
    Document type Article ; Online
    ISSN 2379-5042
    DOI 10.1128/msphere.00203-20
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: The continued epidemic threat of SARS-CoV-2 and implications for the future of global public health

    Sheahan, Timothy P / Frieman, Matthew B

    Current Opinion in Virology

    2020  Volume 40, Page(s) 37–40

    Keywords Virology ; covid19
    Language English
    Publisher Elsevier BV
    Publishing country us
    Document type Article ; Online
    ZDB-ID 2611378-8
    ISSN 1879-6265 ; 1879-6257
    ISSN (online) 1879-6265
    ISSN 1879-6257
    DOI 10.1016/j.coviro.2020.05.010
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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