Targeting SARS-CoV-2 Using Polycomb Inhibitors as Antiviral Agents

Ayaz, Sameer; Crea, Francesco

doi:10.2217/epi-2020-0154

Cited by 12 publications

(12 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was reported that pathogenic influenza viruses and coronaviruses control IFN‐stimulated gene responses by polycomb repressive complex 2‐mediated H3K27me3 at the promoter region of certain IFN‐stimulated genes (Menachery et al, 2014). It is not yet known whether SARS‐CoV‐2 uses the same epigenetic mechanisms, but potential epigenetically regulated factors have been reported, and it would be worth exploring these to find out successful treatment strategies as hypothesized by Ayaz and Crea (2020).…”

Section: Epigenetic Factorsmentioning

confidence: 99%

Genetic and epigenetic factors associated with increased severity of Covid‐19

Yildirim

Sahin

Yazar

et al. 2021

Cell Biology International

View full text Add to dashboard Cite

Since December 2019, a new form of severe acute respiratory syndrome (SARS) from a novel strain of coronavirus (SARS coronavirus 2 [SARS‐CoV‐2]) has been spreading worldwide. The disease caused by SARS‐CoV‐2 was named Covid‐19 and declared as a pandemic by the World Health Organization in March 2020. Clinical symptoms of Covid‐19 range from common cold to more severe disease defined as pneumonia, hypoxia, and severe respiratory distress. In the next stage, disease can become more critical with respiratory failure, sepsis, septic shock, and/or multiorgan failure. Outcomes of Covid‐19 indicate large gaps between the male–female and the young–elder groups. Several theories have been proposed to explain variations, such as gender, age, comorbidity, and genetic factors. It is likely that mixture of genetic and nongenetic factors interplays between virus and host genetics and determines the severity of disease outcome. In this review, we aimed to summarize current literature in terms of potential host genetic and epigenetic factors that associated with increased severity of Covid‐19. Several studies indicated that the genetic variants of the SARS‐CoV‐2 entry mechanism‐related (angiotensin‐converting enzymes, transmembrane serine protease‐2, furin) and host innate immune response‐related genes (interferons [IFNs], interleukins, toll‐like receptors), and human leukocyte antigen, ABO, 3p21.31, and 9q34.2 loci are critical host determinants related to Covid‐19 severity. Epigenetic mechanisms also affect Covid‐19 outcomes by regulating IFN signaling, angiotensin‐converting enzyme‐2, and immunity‐related genes that particularly escape from X chromosome inactivation. Enhanced understanding of host genetic and epigenetic factors and viral interactions of SARS‐CoV‐2 is critical for improved prognostic tools and innovative therapeutics.

show abstract

Section: Epigenetic Factorsmentioning

confidence: 99%

Genetic and epigenetic factors associated with increased severity of Covid‐19

Yildirim

Sahin

Yazar

et al. 2021

Cell Biology International

View full text Add to dashboard Cite

show abstract

“…Interestingly, the polycomb repressive complex 2 (PRC2), which mediates transcription repression via H3K27me3 enrichment at specific IFN-stimulated genes, could also be considered a target. Pharmacologic inhibitors of PRC2 are currently in advanced clinical trials for cancer treatment and could be easily repurposed to treat COVID-19 patients [ 91 ].…”

Section: Epigenetic Implication In Sars- Cov-2 Infection and Therapymentioning

confidence: 99%

The epigenetic implication in coronavirus infection and therapy

et al. 2020

View full text Add to dashboard Cite

Epigenetics is a relatively new field of science that studies the genetic and non-genetic aspects related to heritable phenotypic changes, frequently caused by environmental and metabolic factors. In the host, the epigenetic machinery can regulate gene expression through a series of reversible epigenetic modifications, such as histone methylation and acetylation, DNA/RNA methylation, chromatin remodeling, and non-coding RNAs. The coronavirus disease 19 (COVID-19) is a highly transmittable and pathogenic viral infection. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which emerged in Wuhan, China, and spread worldwide, causes it. COVID-19 severity and consequences largely depend on patient age and health status. In this review, we will summarize and comparatively analyze how viruses regulate the host epigenome. Mainly, we will be focusing on highly pathogenic respiratory RNA virus infections such as coronaviruses. In this context, epigenetic alterations might play an essential role in the onset of coronavirus disease complications. Although many therapeutic approaches are under study, more research is urgently needed to identify effective vaccine or safer chemotherapeutic drugs, including epigenetic drugs, to cope with this viral outbreak and to develop pre- and post-exposure prophylaxis against COVID-19.

show abstract

“… 123 Interestingly, influenza A viruses, MERS-CoV, and SARS-CoV are able to activate the PRC2, which, in turn, increases the levels of H3K27me3 (repressive mark) at the promoters of targeted IFN-stimulated genes to counteract the host antiviral immune response. 124 This let us suggest that also SARS-CoV-2 might use the same mechanisms to inactive IFN-related pathways in infected cells; besides, since polycomb inhibitors have shown a general antiviral activity, 125 it might be useful to investigate whether hydroxychloroquine can directly impact on PRC2 activity in COVID-19.…”

Section: Epidrug Repurposingmentioning

confidence: 99%

Epigenetic susceptibility to severe respiratory viral infections and its therapeutic implications: a narrative review

Crimi

Benincasa

Figueroa-Marrero

et al. 2020

British Journal of Anaesthesia

View full text Add to dashboard Cite

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 immunerelated transcriptional programmes by regulating chromatin structure and gene expression patterns. Viruses causing severe pulmonary illness can use epigenetic-regulated mechanisms during hostepathogen 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 viralehost interaction during critical illness. In this article, 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.

show abstract

Targeting SARS-CoV-2 Using Polycomb Inhibitors as Antiviral Agents

Abstract: Mechanistically, these viruses activate several epigenetic effectors, including the polycomb repressive complex 2 (PRC2), which mediates H3K27me3 at the promoter of certain IFN-stimulated genes repressing transcription. "

Cited by 12 publications

References 13 publications

Genetic and epigenetic factors associated with increased severity of Covid‐19

Genetic and epigenetic factors associated with increased severity of Covid‐19

The epigenetic implication in coronavirus infection and therapy

Epigenetic susceptibility to severe respiratory viral infections and its therapeutic implications: a narrative review

Contact Info

Product

Resources

About