Glycyrrhizic acid derivatives as influenza A/H1N1 virus inhibitors

Abstract

This Letter describes the synthesis and antiviral activity study of some glycyrrhizic acid (GL) derivatives against influenza A/H1N1/pdm09 virus in MDCK cells. Conjugation of GL with l-amino acids or their methyl esters, and amino sugar (d-galactose amine) dramatically changed its activity. The most active compounds were GL conjugates with aromatic amino acids methyl esters (phenylalanine and tyrosine) (SI=61 and 38), and S-benzyl-cysteine (SI=71). Thus modification of GL is a perspective route in the search of new antivirals, and some of GL derivatives are potent as anti-influenza A/H1N1 agents.

Effects of glycyrrhizic acid (Viusid-Vet® powder) on the reduction of influenza virus spread and on production parameters in pigs

“…The most recently proposed mechanism of action for this substance is its ability to decrease membrane fluidity, as this feature is necessary for the fusion of the viral envelope with the cell membrane in the course of the viral life-cycle. 8 The results here obtained suggest that the constant administration of glycyrrhizic acid as Viusid-Vet® powder enhances the pig's ability to reduce H1N1 and H3N2 viral load. However, on week two there were no differences in the immunological responses between treated and control groups, as assessed with HI.…”

“…[9][10][11][12][13] As in this trial, other authors have also proposed antiviral activity for glycyrrhizic acid. 8,[10][11][12]14 However, the precise manner in which this action is achieved is not known. The most recently proposed mechanism of action for this substance is its ability to decrease membrane fluidity, as this feature is necessary for the fusion of the viral envelope with the cell membrane in the course of the viral life-cycle.…”

“…8 It is already available in the human market, and it is commercialized as a nutraceutical preparation mixed with antioxidants, vitamins and oligoelements (Viusid®, from Catalysis, Spain; distributed by Dermaceutical México, SA de CV Mexico City). Glycyrrhizic acid has been shown to possess in vitro and in vivo antiviral activity that interferes with both DNA and RNA replication, thus interfering with the replication of a wide range of viruses, including herpes, influenza A and B, hepatitis B, coronavirus and SARS [9][10][11][12][13][14] Glycyrrhizic acid and derivatives have been shown to be able to impede the release of virions from their capsids, 14 apparently due to a dose-dependent inhibition of protein kinase P phosphorylation 15,16 and perhaps due to its ability to decrease membrane fluidity.…”

“…Glycyrrhizic acid has been shown to possess in vitro and in vivo antiviral activity that interferes with both DNA and RNA replication, thus interfering with the replication of a wide range of viruses, including herpes, influenza A and B, hepatitis B, coronavirus and SARS [9][10][11][12][13][14] Glycyrrhizic acid and derivatives have been shown to be able to impede the release of virions from their capsids, 14 apparently due to a dose-dependent inhibition of protein kinase P phosphorylation 15,16 and perhaps due to its ability to decrease membrane fluidity. 8 Likewise, glycyrrhizic acid interferes with arylamine N-acetyltransferase activity in bacteria, thus showing antibacterial effects against at least Streptococcus spp., Haemophilus spp., and Klebsiella spp. [17][18][19] Supplementation of antioxidants, vitamins and oligoelements may also have positive effects when mixed as in the commercial preparation Viusid-Vet® powder (Dermaceutical SA de CV, Mexico City).…”

Asteltoxins with Antiviral Activities from the Marine Sponge-Derived Fungus Aspergillus sp. SCSIO XWS02F40

“…Meanwhile, influenza viruses are still a great threat to human health [2,3]. So far, only two classes of antiviral drugs, which include amantadine and the neuraminidase inhibitors, are currently used as anti-influenza therapeutic drugs, but both of them have some adverse side effects in humans as well as the resistance of the virus towards this drug [4,5]. Hence, a concerted effort is aimed at discovering new antiviral agents to treat and eradicate these infectious agents [6,7].…”