By Lori Bystrom
Flu season is still upon us and many of us will fall under influenza’s nasty spell, if we have not already. Folklore suggests that elderberries can ward off evil spirits and many illnesses, and although they may not be the first remedy that comes to mind when you have the flu, these fruits may be worth a second look. Recent research suggests that these dark purple berries have antiviral properties and the mechanisms that contribute to their effects may provide additional clues on how to fight off this winter virus.
Currently, there are relatively few antivirals on the market, and their widespread use has led to increasing resistance and declining efficacy. As a result, scientists are trying to better understand influenza and what confers resistance. Moreover, the specter of a deadly influenza pandemic is leading many researchers to explore diverse and novel treatment options.
Elderberries have a long history of medicinal and dietary use. As well as being used to make pies, jellies, wine and liqueurs, they have also been used to make various medicinal concoctions. These berries have also shown activity against both bacterial and viral pathogens, including several strains of influenza.There are also many commercial preparations of elderberry that are available (e.g., syrups and lozenges), some of which have alleviated flu symptoms in clinical trials.1,2
Despite mounting evidence that elderberries might be valuable for treating the flu, their mechanistic effects are not well understood, especially at the molecular level. Swaminathan et al., demonstrated that an anthocyanin pigment (cyanidin-3-sambubiocide), found in European elderberries (Sambucus nigra), have unique antiviral effects. As with several commercial antivirals, the anthocyanin inhibits viral neuraminidases — enzymes that allow progeny viruses to be released from the host cell. Specifically, viral neuraminidases cleave sialic acid groups, which enable the virus to detach from the host and spread the virus. In a video that demonstrates these effects, the neuraminidases are portrayed as blue monster-like enzymes with teeth that cleave sialic acid groups. This study shows for the first time that cyanidin-3-sambubiocide binds to an active site of influenza neuraminidase and potentially blocks the enzyme’s effects (similar to the yellow objects in the video).
The authors used mass spectrometry to measure the mass fragments released from unbound and anthocyanin-bound neuraminidases. Based on these results, the researchers were able to predict which residues of the influenza neuraminidase bound to the anthocyanin. The precise location was further elucidated by computational studies that evaluated the interaction between the anthocyanin component (excluding sugar groups) and the N1 neuraminidase from the 2009 H1N1 pandemic strain. The antiviral effects of the compound were also confirmed to be effective by a neuraminidase inhibition assay. These experiments indicated that the anthocyanin favored binding to a so-called “430-cavity”, which is different from the region where standard antiviral drugs bind. Furthermore, the results showed that the bound anthocyanin was located away from two residues that that are known to regulate neuraminidase resistance.
Although the results are promising, more research is warranted to confirm that cyanidin-3-sambubiocide has antiviral effects in clinical studies, and whether or not other compounds in elderberries enhance, synergize or alter the activity of this compound. Nevertheless, elderberries may help scientists find more effective and less resistant-prone treatments that may prevent influenza from casting a dark shadow on our health.