Strigolactones as broad-spectrum antivirals against β-coronaviruses through targeting the main protease Mpro

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 Andre;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

2023-01-01

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Abstract

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.