15 Matching Annotations
  1. Jul 2021
    1. targeting it for lysosomal degradation

      In this study, the authors demonstrate that ORF8 SARS-CoV-2 is uniquely capable of forming aggregates when expressed in lung epithelial cells. This aggregation potently inhibits anti-viral protein expression in response to IFNγ, which could contribute to SARS-Co-V2 escape from the host antiviral immune response. DOI: 10.3389/fimmu.2021.679482

    2. monocytes

      However, it has recently been shown that decreased CD4 expression by monocytes correlated with disease severity suggesting SARS-Co-V2 infection could potentially affect function. DOI: 10.1089/vim.2020.0166

    3. KIM-1 inhibitor (TW-37)

      Recent clinical data suggest that KIM-1 can also be used as a biomarker for individuals that will go on to develop acute kidney injury following SARS-Co-V2 infection. DOI: 10.1007/s40620-021-01079-x

    4. correlated with disease progression

      Indeed this distinction between the immune systems of males and females is to be considered when developing vaccines against SARS-Co-V2. (DOI: 10.1021/acs.molpharmaceut.1c00291)

    5. (TMPRSS2)

      The inhibitor of TMPRSS2, N-0385, administered intranasally, has recently been shown to improve clinical outcomes in the severe K18-human ACE2 transgenic mouse model of SARS-CoV-2 disease. This is another potential novel therapeutic for patients suffering with COVID-19 (DOI: 10.1101/2021.05.03.442520).

    6. HMGB1, which was demonstrated to be crucial for viral entry

      Indeed, a recent paper has shown that an inihibitor of HMGB1, glycyrrhizin, can simultaneously stop virus replication and suppress proinflammatory mediators. This evidence provides a potential new therapeutic option for COVID-19 patients (DOI: 10.1016/j.cyto.2021.155496).

  2. Apr 2021
    1. SARS-CoV-2 ORF7a was shown to counteract tetherin to allow viral release [77]. SARS-CoV-2 ORF8

      ORF8 appears to have originated from ORF7a https://doi.org/10.1128/mBio.03014-20 and the crystal structure of both proteins reveals a very similar core structure https://doi.org/10.1073/pnas.2021785118 , which may suggest that some of the functions for these accessory proteins could be similar or redundant.

    2. 8 T-cells

      and to inhibit the production of INFß https://doi.org/10.1016/j.virusres.2021.198350

    3. targeting the type I IFN pathway

      SARS-CoV-2 ORF9b facilitates viral replication by targeting multiple innate sensing pathways depleting type I and III IFN signalling. ORF9b interacts with RIG-I, MDA-5, MAVS, TRIF, STING and TBK1 and blocks IRF3 phosphorylation and nuclear translocation. https://doi.org/10.1002/jmv.27050

    4. 49

      Published now in J. Virol:

      Rebendenne A, Valadão ALC, Tauziet M, Maarifi G, Bonaventure B, McKellar J, Planès R, Nisole S, Arnaud-Arnould M, Moncorgé O, Goujon C. SARS-CoV-2 triggers an MDA-5-dependent interferon response which is unable to control replication in lung epithelial cells. J Virol. 2021 Jan 29:JVI.02415-20. doi: http://doi.org/10.1128/JVI.02415-20 Epub ahead of print. PMID: 33514628.

    5. Viruses have evolved mechanisms to evade the activation of host innate immune responses

      ORF3 directly impairs DNA sensing by binding to STING and blocking nuclear accumulation of p65 to inhibit NF-kB signalling. Also, the main viral protease of SARS-CoV-2 can inhibit RIG-I receptor (RLR) and STING. https://doi.org/10.1038/s41392-021-00515-5

    6. MDA-5

      The IFN response is activated by SARS-CoV-2 viral intermediates through MDA5-mediated sensing. In lung epithelial cells, MDA5 and LGP2 govern the innate immune response with transcription factors IRF3, IRF5, and NF-κB/p65 regulating IFN pathways in SARS-CoV-2 infection. https://doi.org/10.1016/j.celrep.2020.108628

    7. OVID-19 [17]

      Lipid metabolism can also influence infection as HDL-scavenger receptor B type 1 (SR-B1) facilitates entry into ACE2-expressing cells.The mechanism involve SARS-CoV-2 S1 subunit binding to cholesterol and to HDL components to enhance viral uptake. SR-B1 is co-expressed with ACE2 in different tissues including the human lung. http://doi.org/10.1038/s42255-020-00324-0

    8. .

      TMPRSS4 has also been reported to facilitate virus entry by enhancing SARS-CoV-2 spike fusogenic activity. https://doi.org/10.1126/sciimmunol.abc3582

    9. lysosomal

      A Genome-wide CRISPR screen identified lysosomal protein TMEM106B as a host factor to facilitate infection uniquely to SARS-CoV-2, and not involved in other coronavirus infections. http://doi.org/10.1016/j.cell.2020.12.004