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.

Highlights

  • For SARS-CoV-2 experiments, a strain isolated from a COVID-19 positive patient at the beginning of the pandemic in Italy was used [18] in the Biosafety level 3 facility of the Istituto Superiore di Sanita’ (ISS) in Rome

  • In order to study the antiviral activity of Polydatin and A5+ compounds against influenza virus or SARS-CoV-2, firstly the range of concentrations without cytotoxic effects on cell monolayers was established

  • Vero E6 cell line was treated with different concentrations (5 to 100 μg/mL) of polydatin or A5+ and results were analyzed of treatment

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Summary

Introduction

Viral and microbial infections have been the most feared and dangerous killers, as recently confirmed by the coronavirus disease 2019 (COVID-19). The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) pandemic has caused close to 5 million deaths worldwide Biomedicines 2021, 9, 1721 of people are still dying from this infection and its complications [1]. Remdesivir is an antiviral agent which has been reported to reduce SARS-CoV-2 replication in both in vitro and ex vivo models [2]. As a result of viral evolution, SARS-CoV-2 variants have spread widely and have displayed evidence for being more transmissible, causing more severe disease and/or reducing neutralization by antibodies generated during previous infection or vaccination [3]. The need for additional strategies to fight COVID-19 is evident

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