The emerging role of miRNAs in the pathogenesis of COVID-19: Protective effects of nutraceutical polyphenolic compounds against SARS-CoV-2 infection

Yang, Ce; Chen, Yu-Hsuan; Liu, Pei-Jung; Hu, Wan-Chung; Lu, Kuo‐Cheng

doi:10.7150/ijms.76168

Cited by 15 publications

(14 citation statements)

References 155 publications

(218 reference statements)

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“…Cellular ACE2 and TMPRSS2 expression are considered as main points of entry for SARS-CoV-2 [ 10 ]. Interestingly, microRNAs are also involved in COVID19 pathogenesis, targeting both ACE2 and TMPRSS2 [ 11 , 12 ]. Total ACE2, glycosylated ACE2, and TMPRSS2 protein expression was shown to be overexpressed in cardiomyocytes from autopsy cardiomyocytes of patients with DM compared with non-DM patients.…”

Section: Discussionmentioning

confidence: 99%

Glycated hemoglobin level dynamics in COVID-19 survivors: 12 months follow-up study after discharge from hospital

et al. 2022

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Introduction One of the stages of reproduction of SARS-CoV-2 is the S-protein glycosylation to facilitate penetration into target cells. It has been suggested that SARS-CoV-2 is able to enter erythrocytes, interact with heme and porphyrin, which could influence HbA1c levels. Assessment of HbA1c levels in individuals with acute COVID-19 and after recovery may show clinical relevance of this hypothesis. Aim To assess HbA1c levels in patients with COVID-19 in the acute phase and in early (6–8 weeks) and late (52±2 weeks) periods after recovery. Materials and methods We conducted a multicenter prospective study, which included patients hospitalized in Endocrinology Research Centre and the City Clinical Hospital № 52" diagnosed with COVID-19, virus identified/ not identified. Patients were divided into three groups according to baseline HbA1c level and the presence or absence of previous history of diabetes previous history of diabetes mellitus (DM): HbA1c ≤ 6.0%, HbA1c > 6.0% and patients with DM. Patients were examined during the acute COVID-19 phase and in early (6–8 weeks) and late (52±2 weeks) periods after recovery. Oral glucose tolerance test was performed in the group with initial HbA1c > 6.0% to clarify the diagnosis. Results We included 194 patients in the study. During the follow-up, 52 patients were examined in 6–8 week period: 7 with HbA1c ≤ 6.0%, 34 with HbA1c > 6.0%, 11—with previously diagnosed DM. Carbohydrate metabolism assessment in the later stages (52±2 weeks) after recovery was performed in 78 patients: 33 patients with HbA1c ≤ 6.0%, 36 patients with HbA1c > 6.0% and 9 patients with previously established diabetes. HbA1c median in patients with HbA1c ≤ 6.0% was 5.7% [5.3;5.8], with HbA1c>6.0% -6.4% [6.2; 6.6], with previously diagnosed DM—7.7% [7.2; 8.9]. Statistically significant decrease in HbA1c over time 6–8 weeks after extracts were obtained in both groups of individuals without a history of DM (Wilcoxon test, p<0.05). After 52±2 weeks we observed HbA1c decrease in all three groups (Fridman test, p<0.05): in patients with HbA1c ≤ 6.0% median HbA1c was 5.5[5.3;5.7], with HbA1c>6.0% - 6.1[6.15;6.54], with previously diagnosed DM—7.8 [5.83; 8.08]. Development of DM after 52±2 weeks was recorded in 7.24% of all examined patients without a history of DM, which is 16.6% of the total number of patients examined in dynamics with HbA1c > 6.0%. Conclusion HbA1c elevation during the acute phase of COVID-19 may be false due to the effect of SARS-CoV-2 on hemoglobin kinetics and/or detection on the surface of the SARS-CoV-2 virion highly glycosylated S-proteins by high performance liquid chromatography determinations. Upon detection HbA1c > 6.0% in patients with COVID-19 in the active phase of the disease without concomitant hyperglycemia re-determine the level of HbA1c after recovery is recommended.

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Section: Discussionmentioning

confidence: 99%

Glycated hemoglobin level dynamics in COVID-19 survivors: 12 months follow-up study after discharge from hospital

et al. 2022

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“…These evolving clinically and molecularly evidenced associations between SARS-CoV-2 and CJD underscore an overlapping pathological link between COVID-19 and PrD, both involving systemic inflammation, progressive lethal neurodegeneration, and the potential acceleration of PrD-like protein spread, especially in elderly persons who already possess neurological symptoms. Severe neuroinflammatory reactions and aging are two shared links between neurodegenerative diseases and COVID-19; therefore, COVID-19 patients that have a very high viral load may be at the highest risk of developing long-term adverse neurological consequences [ 13 , 48 , 63 , 64 ].…”

Section: Sars-cov-2 and Prion Disease (Prd): Case Reportsmentioning

confidence: 99%

“…Of considerable interest is the effect of SARS-CoV-2 invasion on the molecular genetics and gene expression patterns of the newly infected host, and this is reflected in part by the consequences of SARS-CoV-2 infection on the abundance, speciation, and complexity of a small family of brain-enriched pathology-associated microRNAs (miRNAs). Very recent evidence suggests that dietary polyphenolic compounds may protect against SARS-CoV-2 invasion by modulating the patterns of expression of host cell miRNA [ 13 , 64 , 65 ]. These ~22-nucleotide single-stranded RNAs (ssRNAs) include several inducible pro-inflammatory miRNAs such as miRNA-146a-5p, miRNA-155-5p, and several others [ 13 , 66 , 67 , 68 , 69 , 70 ].…”

Section: Sars-cov-2 Infection Prd and A Pathological Microrna (Mirna)...mentioning

confidence: 99%

SARS-CoV-2 Invasion and Pathological Links to Prion Disease

et al. 2022

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19 disease, is a highly infectious and transmissible viral pathogen that continues to impact human health globally. Nearly ~600 million people have been infected with SARS-CoV-2, and about half exhibit some degree of continuing health complication, generically referred to as long COVID. Lingering and often serious neurological problems for patients in the post-COVID-19 recovery period include brain fog, behavioral changes, confusion, delirium, deficits in intellect, cognition and memory issues, loss of balance and coordination, problems with vision, visual processing and hallucinations, encephalopathy, encephalitis, neurovascular or cerebrovascular insufficiency, and/or impaired consciousness. Depending upon the patient’s age at the onset of COVID-19 and other factors, up to ~35% of all elderly COVID-19 patients develop a mild-to-severe encephalopathy due to complications arising from a SARS-CoV-2-induced cytokine storm and a surge in cytokine-mediated pro-inflammatory and immune signaling. In fact, this cytokine storm syndrome: (i) appears to predispose aged COVID-19 patients to the development of other neurological complications, especially those who have experienced a more serious grade of COVID-19 infection; (ii) lies along highly interactive and pathological pathways involving SARS-CoV-2 infection that promotes the parallel development and/or intensification of progressive and often lethal neurological conditions, and (iii) is strongly associated with the symptomology, onset, and development of human prion disease (PrD) and other insidious and incurable neurological syndromes. This commentary paper will evaluate some recent peer-reviewed studies in this intriguing area of human SARS-CoV-2-associated neuropathology and will assess how chronic, viral-mediated changes to the brain and CNS contribute to cognitive decline in PrD and other progressive, age-related neurodegenerative disorders.

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“…Studying miRNAs has become crucial for the development of possible diagnostics, prognostics and therapeutics that could help in treatment strategies in the COVID-19 ( Fani et al., 2021 ; Ying et al., 2021 ; Ahmed et al., 2022 ). Several studies aiming to predict miRNAs regulating SARS-CoV-2 pathogenesis were published and various miRNAs are identified that might have an impact on the replication of SARS-CoV-2 ( Chen and Zhong, 2020 ; Marchi et al., 2021 ; Kucher et al., 2022 ; Morales et al., 2022 ; Yang et al., 2022 ). Apart from directly targeting the viral genomes, the miRNAs can indirectly regulate viral replication via regulating host factors that are critical for viral replication.…”

Section: Introductionmentioning

confidence: 99%

“…Apart from directly targeting the viral genomes, the miRNAs can indirectly regulate viral replication via regulating host factors that are critical for viral replication. The expression of proteins implicated in the SARS-CoV-2 life cycle, including ACE2, TMPRSS2, Spike proteins, and Nsp12, can be inhibited by miRNAs ( Yang et al., 2022 ; Paul et al., 2022 ). The type I Interferon pathway is inhibited by SARS-CoV-2 encoded miRNAs, which also regulate the allelic differential expression of vulnerable genes ( Zhu et al., 2021 ).…”

Section: Introductionmentioning

confidence: 99%

In silico analysis of SARS-CoV-2 genomes: Insights from SARS encoded non-coding RNAs

Periwal

Bhardwaj

Sarma

et al. 2022

Front. Cell. Infect. Microbiol.

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The recent pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 has resulted in enormous deaths around the world. Clues from genomic sequences of parent and their mutants can be obtained to understand the evolving pathogenesis of this virus. Apart from the viral proteins, virus-encoded microRNAs (miRNAs) have been shown to play a vital role in regulating viral pathogenesis. Thus we sought to investigate the miRNAs encoded by SARS-CoV-2, its mutants, and the host. Here, we present the results obtained using a dual approach i.e (i) identifying host-encoded miRNAs that might regulate viral pathogenesis and (ii) identifying viral-encoded miRNAs that might regulate host cell signaling pathways and aid in viral pathogenesis. Analysis utilizing the first approach resulted in the identification of ten host-encoded miRNAs that could target the SARS, SARS-CoV-2, and its mutants. Interestingly our analysis revealed that there is a significantly higher number of host miRNAs that could target the SARS-CoV-2 genome as compared to the SARS reference genome. Results from the second approach resulted in the identification of a set of virus-encoded miRNAs which might regulate host signaling pathways. Our analysis further identified a similar “GA” rich motif in the SARS-CoV-2 and its mutant genomes that was shown to play a vital role in lung pathogenesis during severe SARS infections. In summary, we have identified human and virus-encoded miRNAs that might regulate the pathogenesis of SARS coronaviruses and describe similar non-coding RNA sequences in SARS-CoV-2 that were shown to regulate SARS-induced lung pathology in mice.

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The emerging role of miRNAs in the pathogenesis of COVID-19: Protective effects of nutraceutical polyphenolic compounds against SARS-CoV-2 infection

Cited by 15 publications

References 155 publications

Glycated hemoglobin level dynamics in COVID-19 survivors: 12 months follow-up study after discharge from hospital

Glycated hemoglobin level dynamics in COVID-19 survivors: 12 months follow-up study after discharge from hospital

SARS-CoV-2 Invasion and Pathological Links to Prion Disease

In silico analysis of SARS-CoV-2 genomes: Insights from SARS encoded non-coding RNAs

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