Potential repurposing of the HDAC inhibitor valproic acid for patients with COVID-19

Eur J Pharmacol. 2021 May 5:898:173988. doi: 10.1016/j.ejphar.2021.173988. Epub 2021 Mar 2.


There is a need for therapeutic approaches to prevent and mitigate the effects of Coronavirus Disease (2019) (COVID-19). The histone deacetylase (HDAC) inhibitor valproic acid, which has been available for the therapy of epilepsy for many years, is a drug that could be repurposed for patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. This article will review the reasons to consider valproic acid as a potential therapeutic to prevent severe COVID-19. Valproic acid could reduce angiotensin-converting enzyme 2 and transmembrane serine protease 2 expression, required for SARS-CoV-2 viral entry, and modulate the immune cellular and cytokine response to infection, thereby reducing end-organ damage. The combined anti-thrombotic, anti-platelet, and anti-inflammatory effects of valproic acid suggest it could be a promising therapeutic target for COVID-19.

Keywords: Acute respiratory distress syndrome; COVID-19; Histone deacetylase inhibitor; Severe acute respiratory syndrome; Valproic acid.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • COVID-19 / prevention & control
  • COVID-19 Drug Treatment*
  • Drug Repositioning
  • Fibrinolytic Agents / therapeutic use*
  • Histone Deacetylase Inhibitors / therapeutic use*
  • Humans
  • Platelet Aggregation Inhibitors / therapeutic use*
  • SARS-CoV-2*
  • Valproic Acid / therapeutic use*


  • Anti-Inflammatory Agents
  • Fibrinolytic Agents
  • Histone Deacetylase Inhibitors
  • Platelet Aggregation Inhibitors
  • Valproic Acid