This study aims to determine which FDA-approved compound(s) can be repurposed as a broad-spectrum antiviral drug(s) against SARS-CoV-2 and variants. Drug repurposing is a widely used strategy for identifying new uses for approved or investigational drugs that are not covered by the approved or investigational indication. Numerous currently available drugs, including Remdesivir, Dexamethasone, and hydroxychloroquine, have been evaluated for their efficacy in treating COVID-19 to combat the pandemic. However, the applicability of these drugs is limited by efficacy and safety concerns. As the pandemic progresses, the SARS-CoV-2 virus evolves globally, necessitating the development of broad-spectrum antiviral drugs via drug repurposing strategies.
By using pseudotyped and authentic SARS-CoV-2 strains, this study determined that the phenothiazine compounds trifluoperazine 2HCl and thioridazine HCl could potently inhibit SARS-CoV-2 entry with low cytotoxicity. Additionally, these two compounds exhibit broad antiviral activity against the SARS-CoV-2-WH01, B.1.617.2 (Delta), and B.1.1.529 (Omicron) virus strains.
Trifluoperazine 2HCl and thioridazine HCl were initially identified as phenothiazine compounds capable of inhibiting the entry of SARS-CoV-2 and its circulating variants with minimal cytotoxicity. Phenothiazine compounds may be a promising drug lead for the development of effective and broad-spectrum COVID-19 cures.