AUTHOR=Baroni Sara , Carletti Tea , Donalisio Manuela , Arduino Irene , Cazzaniga Irene , Giorgino Toni , Esposito Francesca , Porta Alessia , Diomede Luisa , De Luigi Ada , Gobbi Marco , Lembo David , Marcello Alessandro , Tramontano Enzo , Milani Mario , Mastrangelo Eloise 

TITLE=The antipsychotic drug lurasidone inhibits coronaviruses by affecting multiple targets

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 14 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2024.1487604

DOI=10.3389/fcimb.2024.1487604

ISSN=2235-2988

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.