Epigenetics outside of Viral mutations explains Covid pathogenicity


The article "Epigenetic mechanisms regulating COVID-19 infection" discusses the role of epigenetics in the susceptibility and severity of COVID-19 infection. Epigenetic changes are alterations in gene expression that do not involve changes in the DNA sequence as apposed to NeoDarwinian mutations. They can be caused by environmental factors, such as diet, stress, and exposure to toxins, or by aging.

The article focuses on the role of epigenetic changes in the regulation of the ACE2 gene. ACE2 is a receptor that the SARS-CoV-2 virus uses to enter cells. The authors of the article found that DNA methylation of the ACE2 gene was associated with increased susceptibility to COVID-19 infection. They also found that age-dependent DNA methylation of the ACE2 gene was associated with increased severity of the disease.

In addition to DNA methylation, the authors also investigated the role of histone modifications in the regulation of the ACE2 gene. Histone modifications are chemical changes that alter the structure of histone proteins, which in turn affect the way DNA is packaged in the nucleus. The authors found that histone acetylation, a type of histone modification that is associated with gene activation, was decreased at the ACE2 gene promoter in patients with COVID-19.

The findings of this study suggest that epigenetic changes play a major role in the susceptibility and severity of COVID-19 infection. Further research is needed to confirm these findings and to identify potential targets for epigenetic therapies for COVID-19.

Here are some of the key takeaways from the article:

  • Epigenetic changes affect the expression of genes involved in the immune response to COVID-19.

  • DNA methylation and histone modifications can both affect the expression of the ACE2 gene, which is a receptor that the SARS-CoV-2 virus uses to enter cells.

  • Age-dependent DNA methylation of the ACE2 gene is associated with increased severity of COVID-19.

  • Histone acetylation at the ACE2 gene promoter is decreased in patients with COVID-19.

  • Epigenetic changes may be a potential target for therapies to prevent or treat COVID-19.

Older theories relied on the mutational models of the viruses however they do not explain the full spectrum of viral illnesses. 

Article snippets

Structural analyses have elucidated hot spots in viral binding domains, mutations, and specific proteins in the host.

epigenetic changes that regulate chromatin structure have shown a major impact in genome stabilization and maintenance of cellular homoeostasis and they have been implicated in the pathophysiology of the virus

Epigenetic research has revealed that global DNA methylation along with ACE2 gene methylation and post-translational histone modifications may drive differences in host tissue-,

modulation of the host cells epigenetic landscape following infection represents a molecular tool used by viruses to antagonize cellular signalling

we provide an update of the main research findings at the interface of epigenetics and coronavirus infection.

epigenetic factors that interfere with viral replication and infection and may contribute to COVID-19 susceptibility, offering new ways of thinking in respect to host viral response.

Emerging experimental evidence reveals an interplay of genetic and epigenetic alterations regulating host response

Epigenetic changes that regulate chromatin structure have a major impact in genome stabilization and maintenance of cellular homoeostasis and they have been implicated in the pathophysiology of the virus infection

This type of regulation bridges genotype and phenotype by altering the function of the gene locus without changing the underlying DNA sequence.

playing a key role in gene imprinting, X inactivation, and silencing of the expression of repeated elements and transposons, ensuring genomic stability

Nowadays, more than 160 modifications have been identified

SARS-CoV-2

exhibits 50% homology with Middle East respiratory syndrome coronavirus (MERS-CoV)

cross-species transmission is possible resulting in human outbreaks.

virus entering point at the host cell is the Angiotensin-converting Enzyme 2 (

Once the virus enters the host cell, it replicates a genomic RNA that consists of nine experimental validated open reading frames (ORFs)

a series of comorbidities have been detected in patients who died of COVID-19 infection, including hypertension, lupus, diabetes, cancer, and chronic obstructive lung disease

ACE2 expression is significantly lower in paediatric samples, reflecting the lack of chromatin accessibility in the ACE2 locus

hypermethylation of ACE2 gene may occur in children lungs,

ACE2 gene has been located on the X chromosome and points towards a closer look of the epigenetically regulated developmental process of X inactivation

However, XCI is incomplete in humans with one-third of X-chromosomal genes been expressed from both active (Xa) and inactive (Xi) X chromosomes in female cells with the genes that escape X inactivation been called ‘escapers

Research studies have recently implicated DNA methylation in the regulation of the ACE2 gene, indicating that the host epigenome may represent a risk factor for COVID-19 infection

showed decreased methylation level during ageing

Previous studies had reported that global DNA methylation levels are reduced during ageing, leading to differential methylation patterns of genes related to inflammation, ageing and immune response

These data could potentially explain the higher morbidity of the virus infection in older individuals and in patients with underlying medical conditions

Taken altogether, an emerging role of epigenetic enzymes and modifications is revealed along with their potential activities in COVID-19 treatment

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