Leonard Lipovich

Bio: Leonard Lipovich is an academic researcher from University of Medicine and Health Sciences. The author has contributed to research in topics: Genome & microRNA. The author has an hindex of 1, co-authored 1 publications receiving 13 citations.

miRCOVID-19: Potential Targets of Human miRNAs in SARS-CoV-2 for RNA-Based Drug Discovery.

Abstract: Sense-antisense interactions of long and short RNAs in human cells are integral to post-transcriptional gene regulation, in particular that of mRNAs by microRNAs. Many viruses, including severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 (the causative agent of coronavirus disease 2019, COVID-19), have RNA genomes, and interactions between host and viral RNAs, while known to be functional in other viral diseases, have not yet been investigated in COVID-19. To remedy this gap in knowledge, we present miRCOVID-19, a computational meta-analysis framework identifying the predicted binding sites of human microRNAs along the SARS-CoV-2 RNA genome. To highlight the potential relevance of SARS-CoV-2-genome-complementary miRNAs to COVID-19 pathogenesis, we assessed their expression in COVID-19-relevant tissues using public transcriptome data. miRCOVID-19 identified 14 high-confidence mature miRNAs that are highly likely to interact with the SARS-CoV-2 genome and are expressed in diverse respiratory epithelial and immune cell types that are relevant to COVID-19 pathogenesis. As a proof of principle, we have shown that human miR-122, a previously known co-factor of another RNA virus, the hepatitis C virus (HCV) whose genome it binds as a prerequisite for pathogenesis, was predicted to also bind the SARS-CoV-2 RNA genome with high affinity, suggesting the perspective of repurposing anti-HCV RNA-based drugs, such as Miravirsen, to treat COVID-19. Our study is the first to identify all high-confidence binding sites of human miRNAs in the SARS-CoV-2 genome using multiple tools. Our work directly facilitates experimental validation of the reported targets, which would accelerate RNA-based drug discovery for COVID-19 and has the potential to provide new avenues for treating symptomatic COVID-19, and block SARS-CoV-2 replication, in humans.

The relative expression of miR-31, miR-29, miR-126, and miR-17 and their mRNA targets in the serum of COVID-19 patients with different grades during hospitalization.

Abstract: The aim of this study was to evaluate the expression of four up/down-regulated inflammatory miRNAs and their mRNA targets in the serum samples of COVID-19 patients with different grades. Also, we investigated the relative expression of these miRNAs and mRNAs during hospitalization. In this cross-sectional study, 5 mL of blood sample were taken from COVID-19 patients with different grades and during hospitalization from several health centers of Yazd, Tehran, and Zahedan province of Iran from December 20, 2020 to March 2, 2021. The relative expression of miRNAs and mRNAs was evaluated by q-PCR. We found that the relative expression of hsa-miR-31-3p, hsa-miR-29a-3p, and hsa-miR-126-3p was significantly decreased and the relative expression of their mRNA targets (ZMYM5, COL5A3, and CAMSAP1) was significantly increased with the increase of disease grade. Conversely, the relative expression of hsa-miR-17-3p was significantly increased and its mRNA target (DICER1) was significantly decreased with the increase of disease grade. This pattern was exactly seen during hospitalization of COVID-19 patients who did not respond to treatment. In COVID-19 patients who responded to treatment, the expression of selected miRNAs and their mRNA targets returned to the normal level. A negative significant correlation was seen between (1) the expression of hsa-miR-31-3p and ZMYM5, (2) hsa-miR-29a-3p and COL5A3, (3) hsa-miR-126-3p and CAMSAP1, and (4) hsa-miR-17-3p and DICER1 in COVID-19 patients with any grade (P < 0.05) and during hospitalization. In this study, we gained a more accurate understanding of the expression of up/down-regulated inflammatory miRNAs in the blood of COVID-19 patients. The obtained data may help us in the diagnosis and prognosis of COVID-19. Trial registration: The ethics committee of Zahedan University of Medical Sciences, Zahedan, Iran. (Ethical Code: IR.ZAUMS.REC.1399.316) was registered for this project.

A Differential Signature of Circulating miRNAs and Cytokines Between COVID-19 and Community-Acquired Pneumonia Uncovers Novel Physiopathological Mechanisms of COVID-19

Abstract: Coronavirus Disease 2019 (COVID-19) pneumonia is a life-threatening infectious disease, especially for elderly patients with multiple comorbidities. Despite enormous efforts to understand its underlying etiopathogenic mechanisms, most of them remain elusive. In this study, we compared differential plasma miRNAs and cytokines profiles between COVID-19 and other community-acquired pneumonias (CAP). A first screening and subsequent validation assays in an independent cohort of patients revealed a signature of 15 dysregulated miRNAs between COVID-19 and CAP patients. Additionally, multivariate analysis displayed a combination of 4 miRNAs (miR-106b-5p, miR-221-3p, miR-25-3p and miR-30a-5p) that significantly discriminated between both pathologies. Search for targets of these miRNAs, combined with plasma protein measurements, identified a differential cytokine signature between COVID-19 and CAP that included EGFR, CXCL12 and IL-10. Significant differences were also detected in plasma levels of CXCL12, IL-17, TIMP-2 and IL-21R between mild and severe COVID-19 patients. These findings provide new insights into the etiopathological mechanisms underlying COVID-19.