The COVID-19 pandemic, in the first seven months, has led to more than 15 million confirmed infected cases and 600,000 deaths. SARS-CoV-2, the causative agent for COVID-19, has proved to be a great challenge for its ability to spread in asymptomatic stages and the diverse disease spectrum it has generated. This has created a challenge of unimaginable magnitude, not only affecting human health and life but also potentially generating a long-lasting socioeconomic impact. Both medical sciences and biomedical research have also been challenged, consequently leading to a large number of clinical trials and vaccine initiatives. While known proteins of pathobiological importance are targets for these therapeutic approaches, it is imperative to explore other factors of viral significance. Accessory proteins are one such trait that have diverse roles in coronavirus pathobiology. Here, we analyze certain genomic characteristics of SARS-CoV-2 accessory protein ORF8 and predict its protein features. We have further reviewed current available literature regarding its function and comparatively evaluated these and other features of ORF8 and ORF8ab, its homolog from SARS-CoV. Because coronaviruses have been infecting humans repeatedly and might continue to do so, we therefore expect this study to aid in the development of holistic understanding of these proteins. Despite low nucleotide and protein identity and differentiating genome level characteristics, there appears to be significant structural integrity and functional proximity between these proteins pointing towards their high significance. There is further need for comprehensive genomics and structural-functional studies to lead towards definitive conclusions regarding their criticality and that can eventually define their relevance to therapeutics development.
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http://dx.doi.org/10.3390/pathogens9090677 | DOI Listing |
J Virol
January 2025
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
The evolution of SARS-CoV-2 pathogenicity has been a major focus of attention. However, the determinants of pathogenicity are still unclear. Various hypotheses have attempted to elucidate the mechanisms underlying the evolution of viral pathogenicity, but a definitive conclusion has yet to be reached.
View Article and Find Full Text PDFBackground: Drivers of COVID-19 severity are multifactorial and include multidimensional and potentially interacting factors encompassing viral determinants and host-related factors (i.e., demographics, pre-existing conditions and/or genetics), thus complicating the prediction of clinical outcomes for different severe acute respiratory syndrome coronavirus (SARS-CoV-2) variants.
View Article and Find Full Text PDFiScience
January 2025
School of Life Sciences, Chongqing University, Chongqing 401331, China.
Severe cases of COVID-19 are associated with immune responses that lead to a surge in inflammatory molecules, resulting in multi-organ failure and death. This significant increase in inflammatory factors is triggered by viral proteins. Open reading frame 8 (ORF8) has received particular attention as a unique accessory protein of SARS-CoV-2.
View Article and Find Full Text PDFMol Biol Res Commun
January 2025
Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.
The recent pernicious COVID-19 pandemic is caused by SARS-CoV-2. While most therapeutic strategies have focused on the viral spike protein, Open Reading Frame 8 (ORF8) plays a critical role in causing the severity of the disease. Nonetheless, there still needs to be more information on the ORF8 binding epitopes and their appropriate safe inhibitors.
View Article and Find Full Text PDFJCI Insight
December 2024
Infection Biology Program, Global Center for Pathogen Research and Human Health, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Patients with immune-mediated inflammatory diseases (IMIDs) like rheumatoid arthritis (RA) are at higher risk for severe COVID-19 and long-term complications in bone health. Emerging clinical evidence demonstrated that SARS-CoV-2 infection reduces bone turnover and promotes bone loss, but the mechanism underlying worsened bone health remains elusive. This study sought to identify specific immune mediators that exacerbated preexisting IMIDs after SARS-CoV-2 exposure.
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