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

Abstract

Backgroundhyaluronic 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.Methodsthe 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.Resultsthe 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.Conclusionsthe 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.

In Vitro Screening for Compounds Derived from Traditional Chinese Medicines with Antiviral Activities Against Porcine Reproductive and Respiratory Syndrome Virus

“…Wang et al [24] demonstrated that chlorogenic acid possessed a substantial inhibitory activity against HBV-DNA replication. Coxsackievirus B5 and herpes simplex virus-1 replication were consistently inhibited by hyaluronic acid, regardless of the time of addition [4]. Our previous study also demonstrated that sodium tanshinone IIA sulfonate could inhibit PRRSV replication during a single replication cycle [23].…”

Tailor‐Made Antimicrobial/Antiviral Star Polymer via ATRP of Cyclodextrin and Guanidine‐Based Macromonomer

“…The antiviral efficiency of CD‐PAM‐ co ‐GPHMG reached to 96.2% at a concentration of 50 ppm. Hyaluronic acid (HA) and anionic or cationic dendrimers have shown antiviral activities against a wide spectrum of viruses, e.g., HSV, coxsackievirus, influenza virus, by blocking the virion's attachment to target cells. However, these antiviral agents were ineffective for ADV .…”

“…Hyaluronic acid (HA) and anionic or cationic dendrimers have shown antiviral activities against a wide spectrum of viruses, e.g., HSV, coxsackievirus, influenza virus, by blocking the virion's attachment to target cells. However, these antiviral agents were ineffective for ADV . It is obvious that the polymer can be used as potent virucidal agents against ADV below their toxic concentration to mammalian cells.…”

Antivirals against animal viruses

“…Medical uses of hyaluronic acid include wound healing and mouth care, as well as the treatment of conditions such as joint pain, kerato-conjunctivitis, asthma, and gastritis. This compound, in addition, displays antiviral activity against a variety of DNA and RNA viruses [201]. But, despite its positive effects, the fact that hyaluronic acid could enhance blood-brain barrier permeability, either transcellularly, paracellularly or through infected phagocytes [202], considerably limits its medical uses.…”