title: In vitro evaluation of antiviral and virucidal activity of a high molecular weight hyaluronic acid.
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.
authors: Department of Public Health Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors: Claudio
authors: C
authors: Cermelli
authors: Alessandro
authors: A
authors: Cuoghi
authors: Monica
authors: M
authors: Scuri
authors: Clotilde
authors: C
authors: Bettua
authors: Rachele G
authors: RG
authors: Neglia
authors: Andrea
authors: A
authors: Ardizzoni
authors: Elisabetta
authors: E
authors: Blasi
authors: Tommaso
authors: T
authors: Iannitti
authors: Beniamino
authors: B
authors: Palmieri
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008970:Molecular Weight; D014777:Virus Diseases / Q000821:virology; D014780:Viruses / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D006820:Hyaluronic Acid