Understanding Molecular actions may be the key in Treating Severe Covid-19 cases
A recent study at the Bar Ilan University has found that RNA molecules play a significant regulatory function in immune response role in immune response, and their understanding their interactions might be a target of precision medicine.
June 4th, 2021: Scientific studies rarely focus on long non-coding RNA molecules (lncRNAs), even though they potentially regulate several diseases.In a recent study conducted at the Azrieli Faculty of Medicine of Bar-Ilan University, researchers have reported the role of several lncRNAs in anti-viral inflammatory response regulation.Considering their significant regulatory function in immune response, the researchers sought to identify lncRNAs co-expressed with human genes involved in immune-related processes during severe SARS-CoV-2 infection in the lungs.
Recent studies demonstrated that patients afflicted with severe SARS-CoV-2 infections present increased levels of pro-inflammatory plasma cytokines, as opposed to milder cases, highlighting the release of inflammatory cytokines as being central to COVID-19 severity. However, the underlying molecular mechanisms responsible for dysfunctional immune responses during COVID-19 infection remain elusive.
In a paper recently published in the journal Viruses, the researchers demonstrated that lncRNAs are indeed potential regulators of anti-viral response during severe SARS-CoV-2 infection. Using the available transcriptome data from the lung cells of severely affected COVID-19 patients and SARS-CoV-2 infected lung-cell-lines, they constructed a gene co-expression network that can measure the relationship of gene expression patterns across a group of samples. This analysis enables them to identify four differentially expressed lncRNAs that are found to be strongly correlated to the protein-coding genes in a novel network enriched for different immune-related processes associated with dysregulated cytokine production. These four lncRNAs were also identified as “hubs” – important nodes in this co-expression network, signifying their association with cytokine over-production due to fierce immune response.
The finding suggests that the aberrant expression of lncRNAs can be associated with cytokine storms and anti-viral responses during severe SARS-CoV-2 infection. Thus, the present study uncovers the potential associations of lncRNAs in cytokine and interferon signaling during the response to severe SARS-CoV-2 infection in the lungs. This could provide valuable insight into pro-inflammatory cytokine production and how to mitigate it. It could also potentially be utilized as a future drug target to combat the hyper-inflammation caused by SARS-CoV-2 infection.
“It is remarkable that a major part of the human genome is filled in by non-coding regulatory elements, formerly known as “junk DNA”. Among these are the long non-coding RNAs (lncRNAs). These lncRNAs are receiving more and more recognition as the potential regulators of several diseases,” says Dr. Milana Frenkel-Morgenstern, of Bar-Ilan University’s Azrieli Faculty of Medicine, who led the study with Prof. David Karasik.
This study sheds light on the mechanisms behind COVID-19 severity and dysfunctional immune responses. Understanding the molecular interactions behind the immune dysfunction during severe COVID-19 infection in the lungs should help inform the design and development of novel approaches for treating severe COVID-19 patients.
The researchers plan to validate their findings on human samples and further aim to determine which drugs from their COVID-19 drug database may inhibit the cytokine storm generation in COVID-19and will design experiments to test the efficacy of those drugs.
This study was supported by a grant from the COVID-19 Data Science Institute (DSI) at Bar-Ilan University and a PBC fellowship for outstanding postdoctoral researchers from China and India (to Dr. Sumit Mukherjee, who participated in the research) from the Israel Council for Higher Education.
ABOUT STUDY IN ISRAEL:
The Council for Higher Education of Israel launched the Study in Israel initiative to promote internationalization in the Israeli higher education system and attract international students. The initiative focuses on increasing awareness of Israel’s excellent academia and research while communicating the distinctive, engaged approach to education that Israel offers students. Through “Study in Israel” students from all over the world are invited to “Engage in Excellence”. For further information, log onto – https://studyisrael.org.il/