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

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Abstract
The current SARS-CoV-2 pandemic and the likelihood thatnew coronavirusstrains will emerge in the immediate future point out the urgent needto identify new pan-coronavirus inhibitors. Strigolactones (SLs) area class of plant hormones with multifaceted activities whose rolesin 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 syntheticSLs TH-EGO and EDOT-EGO impair & beta;-coronavirus replication includingSARS-CoV-2 and the common cold human coronavirus HCoV-OC43. Interestingly, in silico simulations suggest the binding of SLs in theSARS-CoV-2 main protease (M-pro) active site, and this wasfurther confirmed by an in vitro activity assay.Overall, our results highlight the potential efficacy of SLs as broad-spectrumantivirals against & beta;-coronaviruses, which may provide the rationalefor repurposing this class of hormones for the treatment of COVID-19patients.
Funding Information
  • Università degli Studi di Torino (RILO2020, RILO2021)
  • Fondazione CRT (2019.2273, 2021.1745)
  • Ministero dell'Università e della Ricerca (2017ALPCM, CUP D13C22003520001, PE00000007)

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