Abstract
The frequent emergence of drug resistant influenza viral strains emphasizes the urgent and continual need to develop new antiviral drugs. Given the encouraging findings of previous studies on antiviral compounds from plant sources, this study focused on medicinal plants from Borneo that were traditionally used to treat symptoms of influenza infection. Following the promising results of earlier investigations, four plant extracts that demonstrated multiple modes of viral inhibition were studied against wild-type and neuraminidase (NA) inhibitor-resistant strains of Types A and B influenza viruses. The extracts exhibited more pronounced activities against the wild-type viruses than the NA inhibitor-resistant strains. Variations in the antiviral potential of the extracts collected from different parts of the same plant were also evidenced in the in vitro micro-inhibition assays. Even though all plant extracts affected NA activity of all viruses, only two extracts demonstrated hemagglutination inhibitory (HI) activities against Type A pandemic H1N1 and Type B viruses. Furthermore, Receptor Destroying Enzyme (RDE) treatments of extracts exhibiting HI activities indicated the presence of sialic acid (SA)-like component(s) that may be responsible for HI activity. Since the antiviral potential of extracts was not completely suppressed by RDE, the possibility of non SA-like antiviral components cannot be ruled out. Therefore, synergistic activity between SA-like and non SA-like components contained in the plant extracts may be responsible for the demonstrated antiviral potential. The results also indicated the presence of non SA-like components that may act against other viral proteins apart from hemagglutinin (HA) and NA. Hence, this study supports the presence of multiple antiviral components that act against different viral proteins or interfere with different stages of viral replication. Our results suggest that these plant extracts have the potential to be developed as therapeutic agents for the treatment of influenza and could be a solution to the global occurrence of viral strains resistant to NA inhibitors.
Highlights
Infections caused by the influenza virus are a critical public health issue which is reflected by significant mortality in humans during annual epidemics or pandemics occurring typically every 10 to 40 years [1]
Since the extracts were shown to act against the neuraminidase inhibitors (NAIs) drug resistant Type A and Type B influenza viruses, they might serve as potential candidates to treat infections caused by drug resistant viruses
The plant extracts investigated contain both sialic acid (SA) mimics and non SA-like components which appear to work in synergy against the viruses tested
Summary
Infections caused by the influenza virus are a critical public health issue which is reflected by significant mortality in humans during annual epidemics or pandemics occurring typically every 10 to 40 years [1]. The most recent, caused by pandemic human influenza A (H1N1), resulted in 18,449 laboratory-confirmed deaths globally within a period of one and a half years from early April 2009 to August 2010 [2]. Influenza viruses belong to the family Orthomyxoviridae, a family of RNA viruses, and are classified into three types, A, B and C, all of which are known to affect vertebrates, including birds, humans and other mammals [4]. Types A and B viruses are the predominant causes of human influenza infections with Type A being the major causative agent of epidemics [5]. Hemagglutinin (HA) and neuraminidase (NA) are the main glycoproteins of Types A and B viruses [6]; depending on the antigenicity of the two surface glycoproteins, there are currently 17 HA (H1 - H17) and 9 NA (N1 - N9) subtypes recognized in Type A virus, with most subtypes present in waterfowl and shorebirds [7] [8]
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