Naringenin is a powerful inhibitor of SARS-CoV-2 infection in vitro

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Schematic representation of TPC2 role, investigated through genetic ablation and drug blocker, in the inhibition of Coronaviruses release into the cells.

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Naringenin was very effective in inhibiting human coronaviruses infection

Vero E6 cells were treated adding 62.5 μM Nar 1 h before infection with HCoVOC43 and HCoV229E (MOI:0.01). End-point RT/PCR results indicated a strong inhibition of viral replication as shown in Fig. 1A.

TPC2, the molecular target of Naringenin, was critical in regulating HCoV229E infection mechanism

To further assess the involvement of TPC2 in CoV infection we silenced its expression in the human cell line Huh7.5. Cells were pretreated for siRNA-mediated knockdown of TPC2, which was followed by infection with HCoV229E (MOI:0.01). Inhibition of viral replication was determined at 24, 48 and 72 h post-infection (hpi). Partial inhibition of 229E replication was observed at 24 hpi in cells silenced for TPC2 by siRNA while stronger inhibition was observed at 48 and 72 hpi (Fig. 1B). Fig. 1C

Naringenin showed a strong antiviral activity against SARS-CoV-2

Vero E6 cells were infected with SARS-CoV-2 (MOI:0.01) and monitored for the presence of cytopathic effect (CPE) at 48 and 72 hpi. Upon addition of Nar to the external medium, we observed that SARS-CoV-2 infection was inhibited in a time- and concentration-dependent manner (Fig. 1D-E). Images showed that Nar treatment did not cause toxicity on uninfected cells at any of the tested concentrations and DMSO (vehicle) did not significantly affect SARS-CoV-2 replication (Fig. 1D-E). Of note, results

Declaration of Competing Interest

The authors report no declarations of interest

Acknowledgements

This work was supported by a grant to G.A. from the Italian Ministry of Health: COVID-19 A.F. 2020-2021 N. COVID-2020-12371817.

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1

Both authors contributed equally to this manuscript.

2

Both authors contributed equally to this manuscript.

3

G.A., M.C., A.C. and A.F. jointly share senior authorship.

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