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. 2023 Jul 14;9(7):1310-1318.
doi: 10.1021/acsinfecdis.3c00219. Epub 2023 Jun 26.

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

Matteo Biolatti  1 , Marco Blangetti  2 , Melissa Baggieri  3 , Antonella Marchi  3 , Silvia Gioacchini  3 , Greta Bajetto  1   4 , Davide Arnodo  2 , Paola Bucci  3 , Raoul Fioravanti  3 , Maedeh Kojouri  3 , Matteo Bersani  5 , Giulia D'Arrigo  5 , Lydia Siragusa  6   7 , Simone Ghinato  2 , Marco De Andrea  1   4 , Francesca Gugliesi  1 , Camilla Albano  1 , Selina Pasquero  1 , Ivan Visentin  8 , Emilio D'Ugo  3 , Francesca Esposito  9 , Paolo Malune  9 , Enzo Tramontano  9 , Cristina Prandi  2 , Francesca Spyrakis  5 , Fabio Magurano  3 , Valentina Dell'Oste  1
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Strigolactones as Broad-Spectrum Antivirals against β-Coronaviruses through Targeting the Main Protease Mpro

Matteo Biolatti et al. ACS Infect Dis. .

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.

Keywords: HCoV-OC43; Mpro; SARS-CoV-2; antiviral screening; strigolactones.

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