COVID-19 News - ORF8 – Unique Sites Of Immune Regulation Jun 16, 2023 1 year, 1 month, 1 week, 3 days, 21 hours, 45 minutes ago
Unique Sites Of Immune Regulation Of SARS-CoV-2 ORF8 Discovered Including Glycosylated, Lipid-Binding, CDR-Like Domains.
COVID-19 News: Since its emergence in late 2019, the novel coronavirus SARS-CoV-2 has wreaked havoc on global health and the economy. With the virus constantly evolving, containing the epidemic and finding effective treatments remain significant challenges.
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Among the accessory proteins of SARS-CoV-2, ORF8 plays a crucial role in immune regulation, yet its molecular intricacies have remained largely unknown. However, a recent groundbreaking study conducted at Southern Medical University in Guangzhou, China, has shed light on this enigmatic protein, uncovering unique features that may hold the key to understanding immune responses to the virus.
The study team successfully expressed SARS-CoV-2 ORF8 in mammalian cells and used X-ray crystallography to determine its structure at a remarkable resolution of 2.3 Å.
The findings of this study have revealed several novel aspects of ORF8 that provide crucial insights into its immune-related functions.
Firstly, the presence of four pairs of disulfide bonds and glycosylation at a specific residue (N78) were found to be essential for stabilizing the protein structure of ORF8. This structural stability is vital for its proper functioning within the viral context.
Additionally, the study identified a lipid-binding pocket within ORF8, as well as three functional loops that resemble CDR (complementarity-determining region)-like domains. These domains have the potential to interact with immune-related proteins, playing a role in regulating the host immune system.
The discovery of these unique sites in ORF8 adds significant knowledge to our understanding of how the virus evades the immune response.
Furthermore, cellular experiments demonstrated that glycosylation at the N78 residue influences ORF8's ability to bind to monocyte cells, which are a key component of the immune system. This suggests that glycosylation modification plays a crucial role in ORF8's interaction with immune cells, possibly aiding the virus in evading detection by the host immune system.
The implications of these findings are immense, as they provide potential targets for the development of ORF8-mediated immune regulation inhibitors. By understanding the structural details and immune-related function of ORF8, researchers can devise strategies to disrupt its interactions with immune-related proteins, thereby enhancing the immune response against SARS-CoV-2.
Past studies and
COVID-19 News reports have already covered discoveries about the role of the ORF8 proteins in SARS-CoV-2 infections.
https://www.thailandmedical.news/news/covid-19-research-briefs-anti-androgens-and-covid-19,-possible-cytotoxic-t-cell-therap
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https://www.thailandmedical.news/news/covid-19-research-university-of-california-scientist-identify-rapidly-evolving-immune-evasion-protein-sars-cov-2-orf8-
https://www.thailandmedical.news/news/breaking-study-discovers-that-sars-cov-2-orf8-encoded-protein-contains-a-histone-mimic-that-disrupts-human-host-cell-epigenetic-regulation
https://www.thailandmedical.news/news/mayo-clinic-researchers-discover-that-sars-cov-2-orf8-protein-is-the-key-factor-that-is-causing-covid-19-disease-severity
https://www.thailandmedical.news/news/breaking-covid-19-news-french-scientists-uncover-how-sars-cov-2-orf8-protein-causes-dysregulation-of-gene-expression-in-infected-cells
https://www.thailandmedical.news/news/covid-19-news-yale-study-shows-that-omicron-subvariants-are-evolving-further-through-mutations-on-orf8-proteins-to-escape-from-mhc-i-recognition
https://www.thailandmedical.news/news/covid-19-news-study-discovers-that-sars-cov-2-orf8-protein-exhibits-complement-inhibitory-properties-and-damages-innate-immunity
https://www.thailandmedical.news/news/study-finds-orf8-protein-of-sars-cov-2-induces-endoplasmic-reticulum-stress-like-responses-and-facilitates-virus-replication-by-triggering-calnexin
https://www.thailandmedical.news/news/covid-19-news-study-validates-that-sars-cov-2-accessory-proteins-orf6,-orf8,-orf9b-and-orf9c-involved-in-profibrotic-processes
https://www.thailandmedical.news/news/sars-cov-2-sublineages-lacking-orf8-protein-do-not-replicate-in-upper-respiratory-tract,-reducing-transmission-but-increasing-inflammation
The importance of this research cannot be overstated, considering the ongoing COVID-19 pandemic caused by SARS-CoV-2. The continuous mutation of the virus increases its infectivity and may be directly linked to the immune evasion strategies employed by viral proteins. Therefore, gaining a deeper understanding of the molecular intricacies of ORF8 is crucial for developing effective therapeutics.
The study also highlights the need to explore the differences between SARS-CoV-2 and related coronaviruses. By comparing the genetic sequences of SARS-CoV-2 and its predecessors, such as SARS-CoV and MERS-CoV, researchers can pinpoint specific structural changes in viral proteins that may contribute to the unique characteristics of SARS-CoV-2.
In conclusion, the study has uncovered vital information about SARS-CoV-2 ORF8. The discovery of unique sites of immune regulation, including glycosylated, lipid-binding, and CDR-like domains, provides valuable insights into the battle against COVID-19. These findings open up new avenues for developing targeted therapies that can disrupt ORF8-mediated immune evasion, ultimately helping to control the spread of the virus and mitigate the devastating impact of the ongoing pandemic.
The study findings were published in the peer reviewed journal: Microbiology Spectrum
https://journals.asm.org/doi/10.1128/spectrum.01234-23
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