Protective Role of Combined Polyphenols and Micronutrients against Influenza A Virus and SARS-CoV-2 Infection In Vitro

Abstract

Polyphenols have been widely studied for their antiviral effect against respiratory virus infections. Among these, resveratrol (RV) has been demonstrated to inhibit influenza virus replication and more recently, it has been tested together with pterostilbene against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In the present work, we evaluated the antiviral activity of polydatin, an RV precursor, and a mixture of polyphenols and other micronutrients, named A5+, against influenza virus and SARS-CoV-2 infections. To this end, we infected Vero E6 cells and analyzed the replication of both respiratory viruses in terms of viral proteins synthesis and viral titration. We demonstrated that A5+ showed a higher efficacy in inhibiting both influenza virus and SARS-CoV-2 infections compared to polydatin treatment alone. Indeed, post infection treatment significantly decreased viral proteins expression and viral release, probably by interfering with any step of virus replicative cycle. Intriguingly, A5+ treatment strongly reduced IL-6 cytokine production in influenza virus-infected cells, suggesting its potential anti-inflammatory properties during the infection. Overall, these results demonstrate the synergic and innovative antiviral efficacy of A5+ mixture, although further studies are needed to clarify the mechanisms underlying its inhibitory effect.

The Protective Effect of a Unique Mix of Polyphenols and Micronutrients against Neurodegeneration Induced by an In Vitro Model of Parkinson’s Disease

“…Then, to avoid side effects, we used a concentration of A5 + lower that 30 μM, and based on cell viability assay, we used 10 μM of A5 + for all further experiments. These results also align with the findings of De Angelis et al [ 22 ].…”

“…Then, we demonstrated that pretreatment with A5 + significantly reduced the levels of IFN-γ (p < 0.05), IL-1β (not significant), IL-6 (p < 0.001), TNF-α (p < 0.001), and CXCL1 (p < 0.001) compared to cells treated only with 6-OHDA. These data are in agreement with our previous data demonstrating that A5 + reduced IL-6 production in Vero E6 cells infected with Influenza A Virus [22], and further suggest relevant anti-inflammatory properties of A5 + .…”

“…Then, to avoid side effects, we used a concentration of A5 + lower that 30 µM, and based on cell viability assay, we used 10 µM of A5 + for all further experiments. These results also align with the findings of De Angelis et al [22]. Similarly, we also tested 6-OHDA toxicity; N1E115 cells were treated with different concentrations of 6-OHDA (10, 30, 50, 75 and 100 µM) for 24 h, and then cell viability was evaluated by performing MTT.…”

“…Based on all these findings, in the present study, we tested the potential neuroprotective effect of a natural patented compound, known as A5 + [ 22 ], a combination of both polydatin and pterostilbene and other beneficial micronutrients mixed together, in an in vitro model of PD. Recently, A5 + mixture has been demonstrated to strongly protect against influenza A virus, and SARS-CoV-2 by a reduction in virus-mediated inflammation [ 22 ].…”

Influenza Virus Down-Modulates G6PD Expression and Activity to Induce Oxidative Stress and Promote Its Replication

“…Indeed, the knockdown of individual sirtuins, including SIRT2, has been shown to increase the influenza virus replication ( Koyuncu et al., 2014 ). Moreover, treatment with sirtuin modulators including resveratrol and its derivatives have been shown to control different respiratory viral infections ( Palamara et al., 2005 ; De Angelis et al., 2021 ; Pasquereau et al., 2021 ). In our model, by restoring the deacetylation activity of SIRT2 using an inhibitor of P300 acetyltransferase (C646), viral replication was reduced ( Figure 6A ).…”