Abstract:Host biomarkers are increasingly being considered as tools for improved COVID-19 detection and prognosis. We recently profiled circulating host-encoded microRNA (miRNAs) during SARS-CoV-2 infection, revealing a signature that classified COVID-19 cases with 99.9% accuracy. Here we sought to develop a signature suited for clinical application by analyzing specimens collected using minimally invasive procedures. Eight miRNAs displayed altered expression in anterior nasal tissues from COVID-19 patients, with miR-1… Show more
“…The low expression level of hsa‐let7b‐5p that we observed in NPS of COVID‐19 patients is in agreement with previous studies, indicating its downregulation in patients with type 2 diabetes mellitus and in inflammation 35–37 . Interestingly, a recent study suggested that, in aged COVID‐19 patients, a lower abundance of miRNAs might be a contributing factor in disease severity 20 . Furthermore, six miRNAs (hsa‐miR‐1‐3p, hsa‐miR‐17‐5p, hsa‐miR‐199a‐3p, hsa‐miR‐429, hsa‐miR‐15a‐5p, and hsa‐miR‐20a‐5p) previously reported to be anti‐viral in respiratory diseases, were downregulated in lung tissues during viral infection but overexpressed in normal lung tissues 13 …”
Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) is the novel coronavirus responsible for worldwide coronavirus disease (COVID‐19). We previously observed that Angiotensin‐converting enzyme 2 (ACE2) and Dipeptidyl peptidase‐4 (DPP4) are significantly overexpressed in naso‐oropharyngeal swabs (NPS) of COVID‐19 patients, suggesting their putative functional role in the disease progression. ACE2 and DPP4 overexpression in COVID‐19 patients may be associated to epigenetic mechanism, such as miRNA differential expression. We investigated if hsa‐let7b‐5p, reported to target both ACE2 and DPP4 transcripts, could be involved in the regulation of these genes. We verified that the inhibition and overexpression of hsa‐let7b‐5p matched to a modulation of both ACE2 and DPP4 levels. Then, we observed a statistically significant downregulation (FC = −1.5; p < 0.05) of hsa‐let7b‐5p in the same COVID‐19 and control samples of our previous study. This is the first study that shows hsa‐let7b‐5p low expression in naso‐oropharyngeal swabs of COVID‐19 patients and demonstrates a functional role of this miR in regulating ACE2 and DPP4 levels. These data suggest the involvement of hsa‐let7b‐5p in the regulation of genes necessary for SARS‐CoV‐2 infections and its putative role as a therapeutic target for COVID‐19.
“…The low expression level of hsa‐let7b‐5p that we observed in NPS of COVID‐19 patients is in agreement with previous studies, indicating its downregulation in patients with type 2 diabetes mellitus and in inflammation 35–37 . Interestingly, a recent study suggested that, in aged COVID‐19 patients, a lower abundance of miRNAs might be a contributing factor in disease severity 20 . Furthermore, six miRNAs (hsa‐miR‐1‐3p, hsa‐miR‐17‐5p, hsa‐miR‐199a‐3p, hsa‐miR‐429, hsa‐miR‐15a‐5p, and hsa‐miR‐20a‐5p) previously reported to be anti‐viral in respiratory diseases, were downregulated in lung tissues during viral infection but overexpressed in normal lung tissues 13 …”
Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) is the novel coronavirus responsible for worldwide coronavirus disease (COVID‐19). We previously observed that Angiotensin‐converting enzyme 2 (ACE2) and Dipeptidyl peptidase‐4 (DPP4) are significantly overexpressed in naso‐oropharyngeal swabs (NPS) of COVID‐19 patients, suggesting their putative functional role in the disease progression. ACE2 and DPP4 overexpression in COVID‐19 patients may be associated to epigenetic mechanism, such as miRNA differential expression. We investigated if hsa‐let7b‐5p, reported to target both ACE2 and DPP4 transcripts, could be involved in the regulation of these genes. We verified that the inhibition and overexpression of hsa‐let7b‐5p matched to a modulation of both ACE2 and DPP4 levels. Then, we observed a statistically significant downregulation (FC = −1.5; p < 0.05) of hsa‐let7b‐5p in the same COVID‐19 and control samples of our previous study. This is the first study that shows hsa‐let7b‐5p low expression in naso‐oropharyngeal swabs of COVID‐19 patients and demonstrates a functional role of this miR in regulating ACE2 and DPP4 levels. These data suggest the involvement of hsa‐let7b‐5p in the regulation of genes necessary for SARS‐CoV‐2 infections and its putative role as a therapeutic target for COVID‐19.
“…In a study on DEGs in peripheral blood samples of patients with SARS-CoV-2, these two miRNAs were deduced as potentially interacting miRNAs 30 . hsa-mir-93-5p was deduced as a signature that may distinguish patients with COVID-19 from healthy individuals 35 . These findings may nominate both miRNAs as candidate biomarkers for the viral infection using only blood samples from the patients.…”
COVID-19 is a global pandemic impacting the daily living of millions. As variants of the virus evolve, a complete comprehension of the disease and drug targets becomes a decisive duty. The Omicron variant, for example, has a notably high transmission rate verified in 155 countries. We performed integrative transcriptomic and network analyses to identify drug targets and diagnostic biomarkers and repurpose FDA-approved drugs for SARS-CoV-2. Upon the enrichment of 464 differentially expressed genes, pathways regulating the host cell cycle were significant. Regulatory and interaction networks featured hsa-mir-93-5p and hsa-mir-17-5p as blood biomarkers while hsa-mir-15b-5p as an antiviral agent. MYB, RRM2, ERG, CENPF, CIT, and TOP2A are potential drug targets for treatment. HMOX1 is suggested as a prognostic biomarker. Enhancing HMOX1 expression by neem plant extract might be a therapeutic alternative. We constructed a drug-gene network for FDA-approved drugs to be repurposed against the infection. The key drugs retrieved were members of anthracyclines, mitotic inhibitors, anti-tumor antibiotics, and CDK1 inhibitors. Additionally, hydroxyquinone and digitoxin are potent TOP2A inhibitors. Hydroxyurea, cytarabine, gemcitabine, sotalol, and amiodarone can also be redirected against COVID-19. The analysis enforced the repositioning of fluorouracil and doxorubicin, especially that they have multiple drug targets, hence less probability of resistance.
Section: Mirnas As Therapeutic Biomarkermentioning
confidence: 99%
“…This shows the marked correlation of miRNA with the COVID-19 existing therapy [73] . Studies have related the positive results from the COVID-19 RT-PCR test to changes in the miRNA profiles in nasal swabs, which could potentially classify the case self-reliantly [65] . Investigations are expanded with larger groups of infected people, including pre-symptomatic, asymptomatic, and infection caused by different variants.…”
Section: Future Headways For the Development Of Mir-therapeuticsmentioning
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
