Treatment with liquid and dried black elderberry reduced viral replication of six Covid-19 variants and significantly inhibited production of “progeny virions” without affecting cell viability, according to study findings, published in Nutraceuticals.
The present trial is the first to establish clinical evidence on the benefits of black elderberry for infection pathogenesis and “suggests an effective inhibition of viral replication independent of the current and possibly future variants of SARS-CoV-2,” the authors write.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is responsible for over 6.6 million deaths and approximately 647 million global cases.
Clinicians are constantly searching for new ways to manage mutating variants and especially those deemed ‘Variants of Concern’ (VoC) that inhibit vaccine or infection-induced anti-viral immune responses, the authors assert.
“Mutations in SARS-CoV-2 VoCs are mainly located within the spike glycoprotein and generally change the interaction with host receptors and thus affect the infectivity, transmissibility or pathogenicity of the virus,” they explain.
Current VoCs include Alpha, Beta, Gamma, Delta, and Omicron variants. Omicron is the most predominant global variant at the moment and of particular concern due to its resistance to all clinically available monoclonal antibodies.
“In comparison to the other VoCs, Omicron variants contain a high number of deletions, insertions, and mutations, especially in the spike protein. In light of the continuing COVID-19 pandemic and the ongoing occurrence of new SARS-CoV-2 variants the development of broadly effective prophylactic and therapeutic countermeasures remains of the utmost importance,” they comment.
Vaccines have limited impact on disease progression (depending on patient age and infection severity, for example), may cause severe side-effects, and can lead to a high risk of drug-resistance, the authors explain.
“Vaccines are valuable but have limitations due to the high mutation rate of viruses, especially for RNA viruses such as SARS-CoV-2. This causes the continuous appearance of escape mutants, which are able to evade vaccine-induced immunity.”
Conversely, natural products demonstrate consistent anti-viral benefits for a variety of viruses. The European fruit extract Black elderberry fruit extract is a natural antiviral and traditional remedy for coughs, cold, and flu. It contains bioactive compounds (phenolic acids), including polyphenols (4.6%) and anthocyanins (3.5%), that have anti-microbial, anti-inflammatory, and anti-aging properties.
Human studies demonstrate reductions significant reductions in the duration and severity of upper respiratory symptoms from common cold or influenza A viral infections (IAV), while in vitro trials demonstrate antiviral activity against influenza B (IBV) and FIV, as well as IAV.
In addition, the fruit contains peptic polysaccharides that stimulate macrophages and dendritic cells and help modulate the immune system.
Liquid and dry European black elderberry extract (ElderCraft) was supplied by Iprona AG/SPA. The former was standardised to a minimum 3.2% anthocyanin and designated EC 3.2 for the purposes of the study, and the spray-dried water extract (designated EC 14) was standardised to 14% anthocyanin.
Extract anthocyanin content was identified as cyanidin-3-sambubioside-5-glucoside, cyanidin-3-sambubioside and cyanidin-3- glucoside, and main polyphenols were chlorogenic acid, rutin and Isoquercetin.
A ‘Wuhan-type’ SARS-CoV-2 variant, and five common Covid-19 strains, were sourced from Michael Schindler (University Hospital in Tubingen, Germany) and injected into Calu-3 human lung cells for incubation and analysis.
Different dilutions of EC 3.2 were added to the cell cultures, one-hour post-infection. Cell culture supernatants were harvested, and virus production analysed after three days.
A dilution of 1:100 of EC 3.2 “almost completely blocked” virus propagation, producing a similar effect to one micrometre (um) of Remdesivir, the authors report.
On the other hand, dried powder (EC 14) dissolved in water exhibited similar activity, with a comparable half-maximal inhibitory concentration (IC50) value of 1:800.
They speculate that cyanidin-3-sambudiocide (the main anthocyanin) inhibited “the active pocket of the IAV neuraminidase”, while other phenolic compounds disrupted production of papain-like protease (crucial for viral replication), as demonstrated in previous studies.
“Such a mechanism might also be responsible for the observed antiviral effect of black elderberry fruit extract and will be the subject of further investigations.”
The authors argue that results provide solid evidence of the beneficial effects of European black elderberry in a “therapeutic setting”, following a SARS-CoV-2 infection.
They conclude: “Their low cytotoxicity and wide availability in nature would make them a readily distributable treatment option for current and future pandemics”.
Published online, January 13, 2023: http://doi.org/10.3900/nutraceuticals3010007
‘European Black Elderberry Fruit Extract Inhibits Replication of SARS-CoV-2 In Vitro’
Authors: Christian Setz, Maria Fröba, Maximilian Große, Pia Rauch, Janina Auth, Alexander Steinkasserer, Stephan Plattner and Ulrich Schubert