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.

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

Matteo Biolatti
First
;
Marco Blangetti;Greta Bajetto;Davide Arnodo;Matteo Bersani;Giulia D’Arrigo;Simone Ghinato;Marco De Andrea;Francesca Gugliesi;Camilla Albano;Selina Pasquero;Ivan Visentin;Cristina Prandi;Francesca Spyrakis
Co-last
;
Valentina Dell’Oste
2023-01-01

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.
2023
1
9
https://pubs.acs.org/doi/full/10.1021/acsinfecdis.3c00219
antiviral screening, strigolactones, HCoV-OC43, SARS-CoV-2, 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 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
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1914710
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