Repurposing disulfiram: An innovative inhibitory approach against a broad spectrum of viruses.

Disulfiram (DSF), an FDA-approved therapeutic agent for alcohol dependence, has recently attracted considerable interest due to its broad-spectrum inhibitory effects against various viruses. Increasing evidence suggests that DSF can inhibit viral replication through two major mechanisms: the inhibition of viral protein catalytic activity and the ejection of Zn2+ from viral proteins. This review comprehensively summarized the molecular mechanisms underlying DSF's antiviral activity against viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), hepatitis C virus (HCV), influenza virus, human immunodeficiency virus (HIV), and Kaposi sarcoma-associated herpes virus (KSHV), with a particular focus on its dual targeting of Cys residues and Zn2+ coordination sites. By synthesizing current findings and emphasizing novel insights, this review aims to provide a foundation for the development of novel antiviral therapeutic strategies and to inspire further research into the repurposing of DSF for combating viral infections.