Resveratrol inhibits rhinovirus replication and expression of inflammatory mediators in nasal epithelia

Significance Statement

Human rhinoviruses (HRV) are responsible for at least 50% of the common colds, a mild, self-limiting upper respiratory tract illness, nonetheless with major economic impact through loss of productivity. HRV infection is also associated with acute otitis media, sinusitis, bronchiolitis, pneumonia, and severe infections, especially in immunocompromised patients and is also the major cause of exacerbations in both asthma and chronic obstructive pulmonary disease.

There are no approved antiviral agents for the prevention or treatment of HRV infection and vaccination is not feasible since more than 100 different rhinovirus types with low antibody cross-reactivity have been described.

Natural bioactive compounds could represent an attractive therapeutic tool to counteract infectious agents. Among natural polyphenols, Resveratrol is of particular interest. It is produced by several plants in response to stress or injury induced by microorganisms or environmental hazards and protects fruits and vegetables against infections. Resveratrol displays a wide range of biological and pharmacological activities including anti-inflammatory, antioxidative, anticancer, antibacterial, antiviral, cardioprotective and neuroprotective effects. Several studies have demonstrated that resveratrol exerts antiviral effect against different viruses, including herpes simplex virus, human cytomegalovirus, varicella- zoster virus, Epstein Barr virus, influenza A virus, respiratory syncytial virus, and HIV, but to date no studies demonstrated an effect of resveratrol on HRV. The study presented here provides evidence for a high, dose-dependent, antiviral activity against HRV replication in human nasal epithelia. Resveratrol also strongly suppresses HRV-induced inflammatory mediators and ICAM-I expression. Carboxymethylated glucan improves the stability of resveratrol and further increases the anti-inflammatory effect of the polyphenol. The possibility that a natural compound can be used to affect viral replication and pro-inflammatory cytokine production represents an ideal therapeutic approach. Such therapy, particularly if topical, could have obvious implications for the treatment of rhinovirus infections and the prevention of complications.

Journal Reference

Antiviral Res. 2015 Nov;123:15-21.

Mastromarino P¹, Capobianco D², Cannata F², Nardis C², Mattia E², De Leo A², Restignoli R³, Francioso A⁴, Mosca L⁴.

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Department of Public Health and Infectious Diseases, Section of Microbiology, Sapienza University, I-00185 Rome, Italy. Electronic address: [email protected].
Department of Public Health and Infectious Diseases, Section of Microbiology, Sapienza University, I-00185 Rome, Italy.
NOOS s.r.l., I-00181 Rome, Italy.
Department of Biochemical Sciences, Sapienza University, I-00185 Rome, Italy.

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Abstract

Human rhinoviruses (HRV), the cause of common colds, are the most frequent precipitants of acute exacerbation of asthma and chronic obstructive pulmonary disease, as well as causes of other serious respiratory diseases. No vaccine or antiviral agents are available for the prevention or treatment of HRV infection. Resveratrol exerts antiviral effect against different DNA and RNA viruses. The antiviral effect of a new resveratrol formulation containing carboxymethylated glucan was analyzed in H1HeLa cell monolayers and ex vivo nasal epithelia infected with HRV-16. Virus yield was evaluated by plaque assay and expression of viral capsid proteins by Western blot. IL-10, IFN-β, IL-6, IL-8 and RANTES levels were evaluated by ELISA assay. ICAM-1 was assessed by Western blot and immunofluorescence. Resveratrol exerted a high, dose-dependent, antiviral activity against HRV-16 replication and reduced virus-induced secretion of IL-6, IL-8 and RANTES to levels similar to that of uninfected nasalepithelia. Basal levels of IL-6 and RANTES were also significantly reduced in uninfected epithelia confirming an anti-inflammatory effect of the compound. HRV-induced expression of ICAM-1 was reversed by resveratrol. Resveratrol may be useful for a therapeutic approach to reduce HRV replication and virus-induced cytokine/chemokine production.

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