This abstract seems to indicate epigenetic medicine is one avenue to fight a vast number of diseases we are faced with. Is this a start to seeing attention paid to epigenetics? Can our team of experts take advantage of the interest in this present time and space???
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438995/
Abstract
The emergence of highly pathogenic strains of influenza virus and coronavirus (CoV) has been responsible for large epidemic and pandemic outbreaks characterised by severe pulmonary illness associated with high morbidity and mortality. One major challenge for critical care is to stratify and minimise the risk of multi-organ failure during the stay in the intensive care unit (ICU). Epigenetic-sensitive mechanisms, including deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) methylation, histone modifications, and non-coding RNAs may lead to perturbations of the host immune-related transcriptional programmes by regulating chromatin structure and gene expression patterns. Viruses causing severe pulmonary illness can use epigenetic-regulated mechanisms during host–pathogen interaction to interfere with innate and adaptive immunity, adequacy of inflammatory response, and overall outcome of viral infections. For example, Middle East respiratory syndrome-CoV and H5N1 can affect host antigen presentation through DNA methylation and histone modifications. The same mechanisms would presumably occur in patients with coronavirus disease 2019, in which tocilizumab may epigenetically reduce microvascular damage. Targeting epigenetic pathways by immune modulators (e.g. tocilizumab) or repurposed drugs (e.g. statins) may provide novel therapeutic opportunities to control viral–host interaction during critical illness. In this review, we provide an update on epigenetic-sensitive mechanisms and repurposed drugs interfering with epigenetic pathways which may be clinically suitable for risk stratification and beneficial for treatment of patients affected by severe viral respiratory infections.
Keywords: coronavirus, COVID-19, epigenetic drugs, epigenetics, host–viral interactions, influenza virus, intensive care, severe acute respiratory syndrome
Editor's key points
- • The authors reviewed the literature and ongoing clinical trials, and show that epigenetic biomarkers may stratify the risk of severe respiratory infection.
- • As deoxyribonucleic acid methylation can be reversed, at least partially, some drugs (curcumin, apabetalone, and repurposed drugs such as statins and tocilizumab) may contribute to better treatment of such patients by interfering with epigenetic pathways.
Over the past two decades, we have experienced the emergence of newly recognised highly pathogenic strains of influenza virus (i.e. influenza A virus subtype H1N1 or swine influenza, and influenza A virus subtype H5N1 or avian influenza) and coronavirus (CoV) (i.e. severe acute respiratory syndrome [SARS]-CoV, Middle East respiratory syndrome [MERS]-CoV, and SARS-CoV-2) responsible for pandemic infections associated with high morbidity and mortality.1, 2, 3, 4, 5 These viruses may cause a wide spectrum of respiratory manifestations associated with massive inflammatory cell infiltration and proinflammatory cytokine/chemokine release resulting in acute lung injury (ALI); acute respiratory distress syndrome (ARDS); and, ultimately, death from multi-organ failure (MOF).6, 7, 8 Molecular mechanisms regulating virus–host interactions can significantly affect the degree and adequacy of both immune and inflammatory responses influencing clinical outcomes.9, 10, 11 For the critical care physicians, to identify and prevent the occurrence of this exuberant inflammatory response and to stratify the risk of MOF in the intensive care unit (ICU) are still major challenges.12
Epigenetics may influence host susceptibility to such viral infections.
13 Deoxyribonucleic acid (DNA) methylation, ribonucleic acid (RNA) methylation, histone tail changes, and also non-coding RNAs are heritable and acquired modifications able to alter gene expression at different levels without any changes in the primary DNA sequence. Epigenetic mechanisms, by regulating chromatin structure and gene expression patterns, modulate host immunity and inflammatory response.
14 In critical illness, such epigenetic modifications can promote the release of proinflammatory cytokines and activation of inflammatory cells, responsible for oxidative stress, endothelial dysfunction, apoptosis, and MOF.
15 Epigenetics can also regulate the interaction between host and multidrug-resistant bacteria.