key: cord-0706430-fclxeeih authors: Ayaz, Sameer; Crea, Francesco title: Targeting SARS-CoV-2 using polycomb inhibitors as antiviral agents date: 2020-06-04 journal: Epigenomics DOI: 10.2217/epi-2020-0154 sha: b5a68aa11ed3aaab93f619062142ed5ad3a0820f doc_id: 706430 cord_uid: fclxeeih nan Pharmacologic inhibitors of PRC2 are currently in advanced clinical trials for several malignancies [8] and could be therefore easily repurposed in the fight against COVID-19. Experiments targeting enhancer of zeste-1 homologue 2 which forms part of the PRC2 complex have shown that this enzyme plays a role in modulating viral replication by inhibiting replication of viruses such as Influenza A and Herpes Simplex 1 Virus using knockdown experiments [9] and small molecule inhibitors [10] . PRC2 inhibitors have also been shown to improve the activation of natural killer cells [11] , which constitute one of the first lines of defence against viral infection [12] . In addition, some studies suggest that PRC2 activity is essential for the correct maturation of B and T lymphocytes [13] . Therefore, inhibitors targeting the PRC2 complex could be used to counteract viral repression of interferon stimulated genes and enhance the adaptive immune response in the case of SARS-CoV-2 infection. When testing the antiviral properties of PRC2 inhibitors, it will be essential to evaluate the optimal timing and duration of treatment and its use in combination with other therapies. In addition, most of the data on PRC2 inhibitors have been collected from cancer models so it will be important to study the role of these and other epigenetic drugs in the specific context of SARS-CoV-2 infection in relevant models. However, we think that the current situation requires every scientist to contribute new and possibly unconventional ideas, in the hope that some will soon produce effective treatments. Potential impact of seasonal forcing on a SARS-CoV-2 pandemic The effect of non-pharmaceutical interventions on COVID-19 cases, deaths and demand for hospital services in the UK: A modelling study Developing Covid-19 Vaccines at Pandemic Speed Exuberant elevation of IP-10, MCP-3 and IL-1ra during SARS-CoV-2 infection is associated with disease severity and fatal outcome Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro Pathogenic influenza viruses and coronaviruses utilize similar and contrasting approaches to control interferon-stimulated gene responses An evolutionarily conserved function of polycomb silences the MHC Class I antigen presentation pathway and enables immune evasion in cancer EZH2 as a therapeutic target for multiple myeloma and other haematological malignancies Enhancer of zeste homolog 2 is a negative regulator of mitochondria-mediated innate immune responses Inhibitors of the histone methyltransferases EZH2/1 induce a potent antiviral state and suppress infection by diverse viral pathogens Ezh2 regulates differentiation and function of natural killer cells through histone methyltransferase activity Natural killer cell responses to viral infection EZH2 function in immune cell development The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.