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Open Access Research

In vitro evaluation of antiviral and virucidal activity of a high molecular weight hyaluronic acid

Claudio Cermelli1, Alessandro Cuoghi1, Monica Scuri2, Clotilde Bettua1, Rachele G Neglia1, Andrea Ardizzoni1, Elisabetta Blasi2, Tommaso Iannitti3* and Beniamino Palmieri4

Author Affiliations

1 Department of Public Health Sciences, University of Modena and Reggio Emilia, Modena, Italy

2 Department of Laboratories, Pathological Anatomy and Legal Medicine, University of Modena and Reggio Emilia, Italy

3 Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow, UK

4 Department of General Surgery and Surgical Specialties, University of Modena and Reggio Emilia, Modena, Italy

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Virology Journal 2011, 8:141  doi:10.1186/1743-422X-8-141

Published: 25 March 2011

Abstract

Background

hyaluronic acid (HA), a non-sulphated glycosaminoglycan, is present in synovial fluid, vitreous humour serum and many connective tissues. Pharmaceutical preparations of HA are used in clinical practice for wound healing, joint pain, kerato-conjunctivitis, asthma, mouth care, oesophageal-reflux, and gastritis. Moreover, it is used as a filler to counteract ageing and facial lipoatrophy. Our study aims at investigating the in vitro antiviral activity of a high molecular weight HA.

Methods

the MTT test was used to rule out the potential toxic effects of HA on the different cell lines used in the antiviral assays. The antiviral activity of HA against Coxsackievirus B5, Herpes Simplex Virus-1, Mumps Virus, Adenovirus-5, Influenza Virus A/H1N1, Human Herpesvirus-6, Porcine Parvovirus, Porcine Reproductive and Respiratory Syndrome Virus was assessed by virus yield assays.

Results

the most effective inhibition was observed against Coxsackievirus B5, with 3Log reduction of the virus yield at 4 mg/ml, and a reduction of 3.5Log and 2Log, at 2 mg/ml and 1 mg/ml, respectively: the selectivity index was 16. Mumps virus was highly inhibited too showing a reduction of 1.7Log at 1 mg/ml and 1Log at 4 mg/ml and 2 mg/ml (selectivity index = 12). The selectivity index for Influenza Virus was 12 with the highest inhibition (1Log) observed at 4 mg/ml. Herpes Simplex Virus-1 and Porcine Parvovirus were mildly inhibited, whereas no antiviral activity was observed with respect to Adenovirus-5, Human Herpesvirus-6, Porcine Reproductive and Respiratory Syndrome Virus. No HA virucidal activity was ever observed against any of the viruses tested. Kinetic experiments showed that both Coxsackievirus B5 and Herpes simplex virus-1 replication were consistently inhibited, not influenced by the time of HA addition, during the virus replication cycle.

Conclusions

the spectrum of the antiviral activity exhibited by HA against both RNA and DNA viruses, known to have different structures (with or without envelope) and replication strategies, suggests a non specific mechanism of action, probably involving cell membrane-virus interaction steps. The results of the kinetic experiments support this hypothesis.