Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection has resulted in a devastating disease pandemic responsible for in excess of 300,000 deaths worldwide in just a few months. The clinical severity of SARS-CoV-2 infection is increased in individuals with certain comorbidities and correlates with increased pulmonary expression of angiotensin-converting enzyme 2 (ACE2), the cellular receptor for SARS-CoV-2. In the absence of an effective vaccine, a critical need exists to identify effective therapies for the management of severe SARS-CoV-2-mediated disease. Recent studies suggest that expression levels of ACE2 may be regulated by a class of drugs referred to as epigenetic regulators (ER). ER are currently in clinically use for a range of medical conditions and could be rapidly repurposed for the effective management of severe SARS-CoV-2-mediated disease. Our studies, conducted in collaboration with Prof Sharon Lewin, Director of The Doherty Institute for Infection and Immunity, Melbourne, will screen and evaluate the potential of 2 classes of ER, the histone deacetylase inhibitors (HDACi) and the demethylating agents (DMA) to regulate ACE2 expression in a pulmonary cell system and correlate these findings with effects on SARS-CoV-2 viral burden. Identification of agents with ACE2 suppressive activity and concurrent attenuation of SARS-CoV-2 viral burden will be flagged for rapid clinical development.
COVID19, Epigenetic, Therapy
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