ABSTRACT
Early disease diagnosis is critical for better management and treatment outcome of patients. Therefore, diagnostic methods should ideally be accurate, consistent, easy to perform at low cost and preferably non-invasive. In recent years, various biomarkers have been studied for the detection of cardiovascular diseases, cerebrovascular diseases, infectious diseases, diabetes mellitus and malignancies. Exosomal microRNA (miRNA) are small non-coding RNA molecules that influence gene expression after transcription. Previous studies have shown that these types of miRNAs can potentially be used as biomarkers for cancers of the breast and colon, as well as diffuse large B-cell lymphoma. It may also be used to indicate viral and bacterial infections, such as the human immunodeficiency virus (HIV), tuberculosis and hepatitis. However, its use in the diagnosis of vector-borne diseases is rather limited. Therefore, this review aims to introduce several miRNAs derived from exosomal plasma that may potentially serve as a disease biomarker due to the body's immune response, with special focus on the early detection of vector-borne diseases.
ABSTRACT
Since the first recorded case of the SARS-CoV-2, it has acquired several mutations in its genome while spreading throughout the globe. In this study, we investigated the significance of these mutations by analyzing the host miRNA binding and virus's internal ribosome entry site (IRES). Strikingly, we observed that due to the acquired mutations, five host miRNAs lost their affinity for targeting the viral genome, and another five can target the mutated viral genome. Moreover, functional enrichment analysis suggests that targets of both of these miRNAs might be involved in various host immune signaling pathways. Remarkably, we detected that three particular mutations in the IRES can disrupt its secondary structure which can consequently make the virus less functional. These results could be valuable in exploring the functional importance of the mutations of SARS-CoV-2 and could provide novel insights into the differences observed different parts of the world.
ABSTRACT
The coronavirus disease 2019 (COVID-19) is an ongoing pandemic caused by an RNA virus termed as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). SARS-CoV-2 possesses an almost 30kbp long genome. The genome contains open-reading frame 1ab (ORF1ab) gene, the largest one of SARS-CoV-2, encoding polyprotein PP1ab and PP1a responsible for viral transcription and replication. Several vaccines have already been approved by the respective authorities over the world to develop herd immunity among the population. In consonance with this effort, RNA interference (RNAi) technology holds the possibility to strengthen the fight against this virus. Here, we have implemented a computational approach to predict potential short interfering RNAs including small interfering RNAs (siRNAs) and microRNAs (miRNAs), which are presumed to be intrinsically active against SARS-CoV-2. In doing so, we have screened miRNA library and siRNA library targeting the ORF1ab gene. We predicted the potential miRNA and siRNA candidate molecules utilizing an array of bioinformatic tools. By extending the analysis, out of 24 potential pre-miRNA hairpins and 131 siRNAs, 12 human miRNA and 10 siRNA molecules were sorted as potential therapeutic agents against SARS-CoV-2 based on their GC content, melting temperature (Tm), heat capacity (Cp), hybridization and minimal free energy (MFE) of hybridization. This computational study is focused on lessening the extensive time and labor needed in conventional trial and error based wet lab methods and it has the potential to act as a decent base for future researchers to develop a successful RNAi therapeutic.
ABSTRACT
A detailed understanding of the molecular mechanism of SARS-CoV-2 pathogenesis is still elusive, and there is a need to address its deadly nature and to design effective therapeutics. Here, we present a study that elucidates the interplay between the SARS-CoV and SARS-CoV-2 viruses' and host's miRNAs, an epigenetic regulator, as a mode of pathogenesis; and we explored how the SARS-CoV and SARS-CoV-2 infections differ in terms of their miRNA-mediated interactions with the host and the implications this has in terms of disease complexity. We have utilized computational approaches to predict potential host and viral miRNAs and their possible roles in different important functional pathways. We have identified several putative host antiviral miRNAs that can target the SARS viruses and also predicted SARS viruses-encoded miRNAs targeting host genes. In silico predicted targets were also integrated with SARS-infected human cell microarray and RNA-seq gene expression data. A comparison between the host miRNA binding profiles on 67 different SARS-CoV-2 genomes from 24 different countries with respective country's normalized death count surprisingly uncovered some miRNA clusters, which are associated with increased death rates. We have found that induced cellular miRNAs can be both a boon and a bane to the host immunity, as they have possible roles in neutralizing the viral threat; conversely, they can also function as proviral factors. On the other hand, from over representation analysis, our study revealed that although both SARS-CoV and SARS-CoV-2 viral miRNAs could target broad immune-signaling pathways; only some of the SARS-CoV-2 miRNAs are found to uniquely target some immune-signaling pathways, such as autophagy, IFN-I signaling, etc., which might suggest their immune-escape mechanisms for prolonged latency inside some hosts without any symptoms of COVID-19. Furthermore, SARS-CoV-2 can modulate several important cellular pathways that might lead to the increased anomalies in patients with comorbidities like cardiovascular diseases, diabetes, breathing complications, etc. This might suggest that miRNAs can be a key epigenetic modulator behind the overcomplications amongst the COVID-19 patients. Our results support that miRNAs of host and SARS-CoV-2 can indeed play a role in the pathogenesis which can be further concluded with more experiments. These results will also be useful in designing RNA therapeutics to alleviate the complications from COVID-19.