Protective Role of Combined Polyphenols and Micronutrients against Influenza A Virus and SARS-CoV-2 Infection In Vitro
Marta De Angelis,
David Della-Morte,
Gabriele Buttinelli,
Angela Di Martino,
Francesca Pacifici,
Paola Checconi,
Luigina Ambrosio,
Paola Stefanelli,
Anna Teresa Palamara,
Enrico Garaci,
Camillo Ricordi,
Lucia Nencioni
Affiliations
Marta De Angelis
Laboratory Affiliated to Istituto Pasteur-Fondazione Cenci Bolognetti, Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy
David Della-Morte
Department of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy
Gabriele Buttinelli
Department of Infectious Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy
Angela Di Martino
Department of Infectious Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy
Francesca Pacifici
Department of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy
Paola Checconi
Department of Human Sciences and Quality of Life Promotion, San Raffaele Roma Open University, IRCCS San Raffaele Roma, 00166 Rome, Italy
Luigina Ambrosio
Department of Infectious Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy
Paola Stefanelli
Department of Infectious Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy
Anna Teresa Palamara
Laboratory Affiliated to Istituto Pasteur-Fondazione Cenci Bolognetti, Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy
Enrico Garaci
Department of Human Sciences and Quality of Life Promotion, San Raffaele Roma Open University, IRCCS San Raffaele Roma, 00166 Rome, Italy
Camillo Ricordi
Cell Transplant Center, Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USA
Lucia Nencioni
Laboratory Affiliated to Istituto Pasteur-Fondazione Cenci Bolognetti, Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy
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.
