In vitro virucidal activity of Echinaforce®, an Echinacea purpurea preparation, against coronaviruses, including common cold coronavirus 229E and SARS-CoV-2

Abstract

Background Coronaviruses (CoVs) were long thought to only cause mild respiratory and gastrointestinal symptoms in humans but outbreaks of Middle East Respiratory Syndrome (MERS)-CoV, Severe Acute Respiratory Syndrome (SARS)-CoV-1, and the recently identified SARS-CoV-2 have cemented their zoonotic potential and their capacity to cause serious morbidity and mortality, with case fatality rates ranging from 4 to 35%. Currently, no specific prophylaxis or treatment is available for CoV infections. Therefore we investigated the virucidal and antiviral potential of Echinacea purpurea (Echinaforce®) against human coronavirus (HCoV) 229E, highly pathogenic MERS- and SARS-CoVs, as well as the newly identified SARS-CoV-2, in vitro. Methods To evaluate the antiviral potential of the extract, we pre-treated virus particles and cells and evaluated remaining infectivity by limited dilution. Furthermore, we exposed cells to the extract after infection to further evaluate its potential as a prophylaxis and treatment against coronaviruses. We also determined the protective effect of Echinaforce® in re-constituted nasal epithelium. Results In the current study, we found that HCoV-229E was irreversibly inactivated when exposed to Echinaforce® at 3.2 μg/ml IC50. Pre-treatment of cell lines, however, did not inhibit infection with HCoV-229E and post-infection treatment had only a marginal effect on virus propagation at 50 μg/ml. However, we did observe a protective effect in an organotypic respiratory cell culture system by exposing pre-treated respiratory epithelium to droplets of HCoV-229E, imitating a natural infection. The observed virucidal activity of Echinaforce® was not restricted to common cold coronaviruses, as both SARS-CoV-1 and MERS-CoVs were inactivated at comparable concentrations. Finally, the causative agent of COVID-19, SARS-CoV-2 was also inactivated upon treatment with 50μg/ml Echinaforce®. Conclusions These results show that Echinaforce® is virucidal against HCoV-229E, upon direct contact and in an organotypic cell culture model. Furthermore, MERS-CoV and both SARS-CoV-1 and SARS-CoV-2 were inactivated at similar concentrations of the extract. Therefore we hypothesize that Echinacea purpurea preparations, such as Echinaforce®, could be effective as prophylactic treatment for all CoVs due to their structural similarities.

Can Echinacea be a potential candidate to target immunity, inflammation, and infection - The trinity of coronavirus disease 2019

“…The immunomodulatory activity of Echinacea induces an antiviral response by influencing PRR, PAMP, and DAMPs. Echinacea have been shown to be effective against rhinoviruses [ 121 ], influenza virus [ 122 ], RSV [ 44 ], herpes virus [ 44 ], adenoviruses [ 44 ], and coronaviruses [ 43 , 123 ]. Another compound, chicoric acid, has also shown potent antiviral effects against herpes simplex, influenza, enterovirus, hepatitis B virus, HIV, vaccinia virus, and vesicular stomatitis virus (VSV)-Ebola [ 124 ].…”

“…It is well-studied, extensively used, widely accessible reputed herbal immunomodulator and antiviral which is gaining importance due to its therapeutic benefits along with preclinical and clinical studies. Among numerous herbal drugs, Echinacea has been proposed as a potential herbal drug candidate for novel coronaviruses [ 38 , 39 , 40 , 41 , 42 ] and a recent experimental ( in vitro ) study, showed that Echinacea has inhibitory activity against SARS-CoV-2 [ 43 ]. It is also considered as a functional food ingredient [ 60 ].…”

“…Among numerous herbal drugs, Echinacea has been suggested as a potential herbal drug candidate for novel coronaviruses [ 38 , 39 , 40 , 41 , 42 ]. In a very recent in vitro study, the virucidal and antiviral activity of Echinaforce® (an extract of E. purpurea containing caftaric acid, chlorogenic acid, cichoric acid, echinacoside and alkamide, adodeca 2E,4E,8Z, 10E/Z tetraenoic acid-isobutylamide) has been showed against human coronavirus (HCoV) 229E, MERS- and SARS coronaviruses including SARS-CoV-2 [ 43 ]. The formulation reported to exhibit virucidal activity and a protective effect in an organotypic respiratory cell culture system against RNA viruses with envelope; HCoV-229E, MERS-CoV, and SARS-coronaviruses including SARS-CoV-2.…”

“…The preparations were also found virucidal against yellow fever virus. However, it did not show any activity against vaccinia virus and minute virus of mice, the DNA viruses, with and without an envelope, respectively [ 43 ]. Recently, in another study, thirty-nine herbal medicines were evaluated based on its benefits/risk assessment following many qualitative or semiquantitative guidelines and suggested that Echinacea could be a promising agent [ 39 ].…”

Prophylaxis for COVID-19: a systematic review

“…Numerous pharmaceuticals and biotechs have joined the race to find vaccines, prophylactic and therapeutic candidates against COVID-19 [ 39 ] and this includes a focus on new candidates. Apart from the candidates identified in this review, other molecules cited in the published literature and in the media as possible prophylactic candidates include existing herbal extracts such as Echinacea [ 40 , 41 ], nicotine [ 42 ], and new molecules including PAC-MAN (prophylactic antiviral CRISPR in human) for viral inhibition [ 43 ] and DARPIN®, multi-target binding neutralizing proteins [ 44 ]. The underrepresentation of new molecules in ongoing RCTs is likely in part due to the relative novelty of this virus, and the necessary time lag to develop new molecules prior to testing them in clinical trials.…”