The antipsychotic drug lurasidone inhibits coronaviruses by affecting multiple targets

Front Cell Infect Microbiol. 2024 Nov 25:14:1487604. doi: 10.3389/fcimb.2024.1487604. eCollection 2024.

Abstract

Coronaviruses (CoVs) share key genomic elements critical for viral replication, suggesting the feasibility of developing therapeutics with efficacy across different viruses. In a previous work, we demonstrated the antiviral activity of the antipsychotic drug lurasidone against both SARS-CoV-2 and HCoV-OC43. In this study, our investigations on the mechanism of action of lurasidone suggested that the drug exhibits antiviral activity by targeting the papain-like protease (PL-Pro) of both viruses, and the Spike protein of SARS-CoV-2, thereby hampering both the entry and the viral replication. In vitro assays demonstrate that lurasidone significantly reduces viral load in infected cells, showing that the drug is a promising candidate for further development as a dual-action antiviral, offering a potential new strategy in the fight against COVID-19 and other coronavirus-related diseases.

Keywords: ACE2 interaction; Spike protein; coronaviruses; dual-target compound; papain-like protease.

MeSH terms

  • Animals
  • Antipsychotic Agents* / pharmacology
  • Antiviral Agents* / pharmacology
  • COVID-19 Drug Treatment
  • Chlorocebus aethiops
  • Coronavirus OC43, Human / drug effects
  • Coronavirus Papain-Like Proteases / metabolism
  • Humans
  • Lurasidone Hydrochloride* / pharmacology
  • SARS-CoV-2* / drug effects
  • Spike Glycoprotein, Coronavirus / metabolism
  • Vero Cells
  • Viral Load / drug effects
  • Virus Internalization / drug effects
  • Virus Replication* / drug effects

Substances

  • Antiviral Agents
  • Lurasidone Hydrochloride
  • Antipsychotic Agents
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • papain-like protease, SARS-CoV-2
  • Coronavirus Papain-Like Proteases

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by EU funding within the NextGeneration EU-MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases (Project no. PE00000007, INF-ACT), and RAS LR07 project VIR-UNICA, F73C22001570002.