Strigolactones as Broad-Spectrum Antivirals against β-Coronaviruses through Targeting the Main Protease M^pro

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 pancoronavirus 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 (M pro ) 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.

Antimicrobial Efficacy of a Vegetable Oil Plasticizer in PVC Matrices

“…For the virus studies, we used the human adenovirus type 5 (HAdV, purchased from the “American Type Culture Collection, ATCC”, VR-5), a clinical isolate of human herpes simplex virus type 1 (HSV-1), kindly provided by Dr. Valeria Ghisetti of the “Amedeo di Savoia” Hospital, Turin, Italy, and the human coronavirus strain OC43 (HCoV-OC43), (ATCC VR-1558), a gift from Prof. David Lembo, Department of Clinical and Biological Sciences, University of Turin, Turin, Italy. The HSV-1 and HAdV were propagated and titrated by plaque assay on African green monkey kidney cells (VERO, ATCC CCL-81), whereas the HCoV-OC43 was handled using human lung fibroblast cells (MRC-5, ATCC CCL-171), as previously described [ 31 , 32 ]. The cells were cultured in Dulbecco’s Modified Eagle’s Medium, supplemented with 10% heat-inactivated fetal bovine serum (FBS), 2 mM glutamine, 1 mM sodium pyruvate, 100 U/mL penicillin, and 100 µg/mL streptomycin sulfate (Sigma-Aldrich, Milan, Italy).…”

Antiherpetic Activity of a Root Exudate from Solanum lycopersicum

“…VERO and HFF cells were seeded in a 96-well culture plate (~30,000 cells/well) and exposed to increasing concentrations of either tomato extract or vehicle control (DMSO/H 2 O mixture 1:1). After 48 h (for VERO) or 144 h (for HFF) of incubation, cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) (Sigma-Aldrich) assay, as previously described [ 30 ].…”

New Thiazolidine-4-One Derivatives as SARS-CoV-2 Main Protease Inhibitors

“…The inhibition of SARS-CoV-2 M pro was measured using a FRET assay, as previously described. Briefly, SARSCoV-2 M pro was expressed and purified as described in Biolatti et al [45]; it was pre-incubated with different concentrations of the compounds at 37 • C for 30 min, in a mixture containing 20 mM Tris−HCl pH 7.3, 100 mM NaCl, 1 mM EDTA, 5 mM TCEP, and 0.1% BSA [10]. Subsequently, 12 µM of FRET substrate (peptide DABCYL-KTSAVLQ↓SGFRKM-EDANS) was added and the reaction was carried out at room temperature for 15 min, after which the fluorescent signal (ex/em 320/480) was acquired using a plate reader (PerkinElmer, Waltham, MA, USA) [46].…”