Strigolactones as Broad-Spectrum Antivirals against β-Coronaviruses through Targeting the Main Protease Mpro

• DOI: 10.1021/acsinfecdis.3c00219
• Publication Date: 2023-06-26T15:20:22Z
• Authors: Matteo Biolatti; Marco Blangetti; Melissa Baggieri; Antonella Marchi; Silvia Gioacchini; Greta Bajetto; Davide Arnodo; Paola Bucci; Raoul Fioravanti; Maedeh Kojouri; Matteo Bersani; Giulia D’Arrigo; Lydia Siragusa; Simone Ghinato; Marco De Andrea; Francesca Gugliesi; Camilla Albano; Selina Pasquero; Ivan Visentin; Emilio D’Ugo; Francesca Esposito; Paolo Malune; Enzo Tramontano; Cristina Prandi; Francesca Spyrakis; Fabio Magurano; Valentina Dell’Oste
• Keywords: HCoV-OC43; antiviral screening, strigolactones, HCoV-OC43, SARS-CoV-2, Mpro; SARS-CoV-2; antiviral screening; strigolactones; hcov-oc43; sars-cov-2; m-pro; 610; COVID-19; 600; Antiviral Agents; 3. Good health; Antiviral screening; Strigolactones; HCoV-OC43; SARS-CoV-2; Mpro; Humans; antiviral screening; strigolactone; Mpro; Peptide Hydrolases

The current SARS-CoV-2 pandemic and the likelihood that new coronavirus strains will emerge in the immediate future point out the urgent need to identify new pan-coronavirus inhibitors. Strigolactones (SLs) are a class of plant hormones with multifaceted activities whose roles in plant-related fields have been extensively explored. Recently, we proved that SLs also exert antiviral activity toward herpesviruses, such as human cytomegalovirus (HCMV). Here we show that the synthetic SLs TH-EGO and EDOT-EGO impair β-coronavirus replication including SARS-CoV-2 and the common cold human coronavirus HCoV-OC43. Interestingly, in silico simulations suggest the binding of SLs in the SARS-CoV-2 main protease (Mpro) active site, and this was further confirmed by an in vitro activity assay. Overall, our results highlight the potential efficacy of SLs as broad-spectrum antivirals against β-coronaviruses, which may provide the rationale for repurposing this class of hormones for the treatment of COVID-19 patients.