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  1. Artikel ; Online: No evidence for basigin/CD147 as a direct SARS-CoV-2 spike binding receptor

    Shilts, Jarrod / Wright, Gavin James

    bioRxiv

    Abstract: The spike protein of SARS-CoV-2 is known to enable viral invasion into human cells through direct binding to host receptors including ACE2. An alternate entry receptor for the virus was recently proposed to be basigin/CD147. These early studies have ... ...

    Abstract The spike protein of SARS-CoV-2 is known to enable viral invasion into human cells through direct binding to host receptors including ACE2. An alternate entry receptor for the virus was recently proposed to be basigin/CD147. These early studies have already prompted a clinical trial and multiple published hypotheses of the role of this host receptor in viral infection and pathogenesis. We sought to independently characterize the basigin-spike protein interaction. After conducting several lines of experiments, we report that we are unable to find evidence supporting the role of basigin as a putative spike-binding receptor. Recombinant forms of both the entire ectodomain and S1 domain of the SARS-CoV-2 spike protein that directly bind ACE2 do not interact with basigin expressed on the surface of human cells. Using specialized assays tailored to detect receptor interactions as weak or weaker than the proposed basigin-spike binding, we report no evidence for direct binding of the viral spike to either of the two common isoforms of basigin. Given the pressing need for clarity on which targets of SARS-CoV-2 may lead to promising therapeutics, we present these findings to allow more informed decisions about the translational relevance of this putative mechanism in the race to understand and treat COVID-19.
    Schlagwörter covid19
    Sprache Englisch
    Erscheinungsdatum 2020-07-26
    Verlag Cold Spring Harbor Laboratory
    Dokumenttyp Artikel ; Online
    DOI 10.1101/2020.07.25.221036
    Datenquelle COVID19

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  2. Artikel ; Online: Author Correction: Establishment, optimisation and quantitation of a bioluminescent murine infection model of visceral leishmaniasis for systematic vaccine screening.

    Ong, Han Boon / Clare, Simon / Roberts, Adam Jonathan / Wilson, Mary Edythe / Wright, Gavin James

    Scientific reports

    2021  Band 11, Heft 1, Seite(n) 8015

    Sprache Englisch
    Erscheinungsdatum 2021-04-07
    Erscheinungsland England
    Dokumenttyp Published Erratum
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-021-87190-2
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Establishment, optimisation and quantitation of a bioluminescent murine infection model of visceral leishmaniasis for systematic vaccine screening.

    Ong, Han Boon / Clare, Simon / Roberts, Adam Jonathan / Wilson, Mary Edythe / Wright, Gavin James

    Scientific reports

    2020  Band 10, Heft 1, Seite(n) 4689

    Abstract: Visceral leishmaniasis is an infectious parasitic disease caused by the protozoan parasites Leishmania donovani and Leishmania infantum. The drugs currently used to treat visceral leishmaniasis suffer from toxicity and the emergence of parasite ... ...

    Abstract Visceral leishmaniasis is an infectious parasitic disease caused by the protozoan parasites Leishmania donovani and Leishmania infantum. The drugs currently used to treat visceral leishmaniasis suffer from toxicity and the emergence of parasite resistance, and so a better solution would be the development of an effective subunit vaccine; however, no approved vaccine currently exists. The comparative testing of a large number of vaccine candidates requires a quantitative and reproducible experimental murine infection model, but the parameters that influence infection pathology have not been systematically determined. To address this, we have established an infection model using a transgenic luciferase-expressing L. donovani parasite and longitudinally quantified the infections using in vivo bioluminescent imaging within individual mice. We examined the effects of varying the infection route, the site of adjuvant formulation administration, and standardised the parasite preparation and dose. We observed that the increase in parasite load within the liver during the first few weeks of infection was directly proportional to the parasite number in the initial inoculum. Finally, we show that immunity can be induced in pre-exposed animals that have resolved an initial infection. This murine infection model provides a platform for systematic subunit vaccine testing against visceral leishmaniasis.
    Mesh-Begriff(e) Animals ; Disease Models, Animal ; Disease Progression ; Leishmania donovani/immunology ; Leishmaniasis Vaccines/administration & dosage ; Leishmaniasis Vaccines/immunology ; Leishmaniasis, Visceral/immunology ; Leishmaniasis, Visceral/parasitology ; Leishmaniasis, Visceral/pathology ; Leishmaniasis, Visceral/prevention & control ; Luminescent Proteins/genetics ; Luminescent Proteins/metabolism ; Mice ; Mice, Knockout ; Mice, Transgenic
    Chemische Substanzen Leishmaniasis Vaccines ; Luminescent Proteins
    Sprache Englisch
    Erscheinungsdatum 2020-03-13
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; 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/s41598-020-61662-3
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel: In silico

    Stepanenko, Nataliia / Wolk, Omri / Bianchi, Enrica / Wright, Gavin James / Schachter-Safrai, Natali / Makedonski, Kiril / Ouro, Alberto / Ben-Meir, Assaf / Buganim, Yosef / Goldblum, Amiram

    Frontiers in cell and developmental biology

    2022  Band 10, Seite(n) 824629

    Abstract: Combined hormone drugs are the basis for orally administered contraception. However, they are associated with severe side effects that are even more impactful for women in developing countries, where resources are limited. The risk of side effects may be ...

    Abstract Combined hormone drugs are the basis for orally administered contraception. However, they are associated with severe side effects that are even more impactful for women in developing countries, where resources are limited. The risk of side effects may be reduced by non-hormonal small molecules which specifically target proteins involved in fertilization. In this study, we present a virtual docking experiment directed to discover molecules that target the crucial fertilization interactions of JUNO (oocyte) and IZUMO1 (sperm). We docked 913,000 molecules to two crystal structures of JUNO and ranked them on the basis of energy-related criteria. Of the 32 tested candidates, two molecules (i.e., Z786028994 and Z1290281203) demonstrated fertilization inhibitory effect in both an
    Sprache Englisch
    Erscheinungsdatum 2022-04-05
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2022.824629
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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