BREAKING! German Study Shows That Phytochemicals From Turmeric Inhibit SARS-CoV-2 In Vitro And Could Be Used As Potential Therapeutics For COVID-19

COVID-19 Herbs: Researchers from University Duisburg-Essen-Germany, Ruhr University Bochum-Germany and the University Hospital at LMU Munich-Germany have in a new study found that phytochemicals extracted from the turmeric root like curcumin, demethoxycurcumin and bisdemethoxycurcumin are able to neutralize the SARS-CoV-2 coronavirus in vitro.

 
To date, the availability of effective and well-tolerated antiviral drugs for the treatment of COVID-19 patients is still very limited.
 
Traditional herbal medicines elicit antiviral activity against various viruses and might therefore represent a promising option for the complementary treatment of COVID-19 patients. The application of turmeric root in herbal medicine has a very long history. Its bioactive ingredient curcumin shows a broad-spectrum antimicrobial activity.
 
The study team investigated the antiviral activity of aqueous turmeric root extract, the dissolved content of a curcumin-containing nutritional supplement capsule, and pure curcumin against SARS-CoV-2.
 
The COVID-19 Herbs study findings showed that turmeric root extract, dissolved turmeric capsule content, and pure curcumin effectively neutralized SARS-CoV-2 at subtoxic concentrations in Vero E6 and human Calu-3 cells.
 
Furthermore, curcumin treatment significantly reduced SARS-CoV-2 RNA levels in cell culture supernatants.
 
The study findings uncover curcumin as a promising compound for complementary COVID-19 treatment. Curcumin concentrations contained in turmeric root or capsules used as nutritional supplements completely neutralized SARS-CoV-2 in vitro.
 
The study data argue in favor of appropriate and carefully monitored clinical studies that vigorously test the effectiveness of complementary treatment of COVID-19 patients with curcumin-containing products.
 
The study findings were published in the peer reviewed journal: Viruses.
https://www.mdpi.com/1999-4915/13/10/1914
 
Thailand Medical News had covered a review of a study by Chinese researchers on the possible usage of curcumin to target the SARS-CoV-2 coronavirus as early as July 2020. https://www.thailandmedical.news/news/must-read-covid-19-supplements-chinese-researchers-in-wuhan-discover-that-curcumin-has-antiviral-effects-on-certain-coronaviruses
 
Curcumin is also one of the ingredients in the formulation of our therapeutic teas COVID-19. https://www.thailandmedical.news/news/new-therapeutic-teas-
 
This new study establishes the potent activity of turmeric root and its bioactive compound curcumin against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 
 
The study team investigated the neutralizing activity of aqueous turmeric root extract, curcumin-containing nutritional supplement capsules, and pure curcumin against SA RS-CoV-2 in vitro at low subtoxic concentrations.
 
The COVID-19 pandemic, which is caused by the spread of SARS-CoV-2, continues to increase morbidity and mortality across the world. To date more than 248 million people globally have been infected with the virus and more than 5.02 million people have died from the virus in the last 21 months. These figures are expected to rise drastically in coming months despite the ongoing global vaccination programme as more and more SARS-CoV-2 variants and sub-variants that are immune evasive emerge and spread.  Mitigation strategies and vaccinations have declined the infection rate and severity but not for long and there are limited therapeutic options that are currently available for treating COVID-19.
 
Despite hesitancy by the Western world and by the greedy Western big pharma conglomerates, traditional herbal medicines are a promising option for the complementary treatment of COVID-19.
 
Interestingly, the rhizome of Curcuma longa, which is more commonly known as turmeric root, is one popular option that is associated with potent antiviral properties. Its active ingredients include curcumin (75%), demethoxycurcumin (20–25%), and bisdemethoxycurcumin (5–15%), all of which have a broad spectrum of bioactivities such as antioxidant, anti-inflammatory, antibacterial, antiviral, antitumor, and hepatoprotective properties.
 
Importantly the antiviral activity of curcumin is established against a variety of viruses including the human immunodeficiency virus (HIV), hepatitis C virus (HCV), Influenza A, and the severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1). Few studies are also exploring its role in COVID-19 patients.
 
The three compounds that were tested for their in vitro efficacy against SARS-CoV-2 in this study included aqueous turmeric root extract, a curcumin-containing nutritional supplement capsule, and curcumin (diferuloylmethane) from Sigma Aldrich.
 
In order to obtain the root extract, the study team reduced the turmeric root into fragments through a grater and centrifuged it to remove the solid components.
 
The team further purified the supernatant by ultracentrifugation.
 
The supplement capsule was dissolved in dimethyl sulfoxide (DMSO) and diluted in the culture medium for use. The study team reported that one capsule contained 640 milligrams (mg) of turmeric powder, 105 mg turmeric extract (containing 99.9 mg curcumin), and 5 mg black pepper (containing 4.7 mg piperine).
 
The curcumin alone was also dissolved and diluted similarly.


Dose-dependent antiviral activity of aqueous turmeric root extract, curcumin-containing nutritional supplement capsules, and curcumin against SARS-CoV-2. Decreasing concentrations of aqueous turmeric root extract (1:8–1:1024 dilution) (A), nutritional supplement capsules (468.8–3.7 µg/mL) (B), and curcumin (125–1 µg/mL) (C) were pre-incubated with 100 TCID50 of SARS-CoV-2 for one hour. Subsequently, each dilution of virus–herb suspensions was incubated on confluent Vero E6 cells grown on a 96-well plate. After 48 h, cells were stained with crystal violet and analyzed regarding cytopathic effects. The half-maximal effective concentration (EC50) was calculated by nonlinear regression using GraphPad Prism. The cytotoxic effect of various concentrations of aqueous turmeric root extract, nutritional supplement capsules, and curcumin toward Vero E6 cells was determined by Orangu Cell Counting Solution (Cell guidance systems) after 48 h. Cell viability was normalized to untreated control cells. The experiment was performed three times independently. Error bars represent the standard error of the mean (SEM).

The study team derived SARS-CoV-2 from an isolate obtained in a clinical nasopharyngeal swab of a patient with COVID-19 who was hospitalized in April 2020 at the University Hospital in Essen. For in vitro experiments, Vero E6 cells and Calu-3 cells were used.
 
In the case of the neutralization assays, different dilutions of the test compounds were preincubated with SARS-CoV-2 before incubation with the Vero E6 cells. Importantly, this is a standard in vitro model in SARS-CoV-2 research.
 
The study team assessed the neutralization efficacy of curcumin against SARS-CoV-2 on human Calu-3 cells by an in-cell enzyme-linked immunosorbent assay (ELISA) (icELISA)-based neutralization test (icNT). Here, incubated cells are treated with SARS-CoV-2 N-specific primary antibody, followed by secondary antibody and substrates.
 
In the case of the cell viability test, the study team performed a colorimetric assay using the Orangu cell-counting solution. For quantifying the genomic SARS-CoV-2 material, the researchers harvested the supernatant from the treated cells and purified the viral ribonucleic acid (RNA). Using primers targeting the viral membrane (M) or nucleocapsid (N) gene, the researchers quantified the SARS-CoV-2 RNA by reverse-transcription qualitative polymerase chain reaction (RT-qPCR).
 
The study team presented the cytopathic effects (CPE) using transmitted light microscopy. In this neutralization of SARS-CoV-2 by aqueous turmeric root extract, curcumin-containing nutritional supplement capsules, and curcumin, using various dilutions, the researchers calculated the concentration required for complete virus neutralization and calculated the EC50 values.

Neutralization of SARS-CoV-2 by aqueous turmeric root extract, curcumin-containing nutritional supplement capsules, and curcumin on a human cell line assessed by an in-cell ELISA (icELISA)-based neutralization test (icNT). (A) Decreasing concentrations of aqueous turmeric root extract (1:16–1:128 dilution), nutritional supplement capsule content (468.8–58.6 µg/mL), or curcumin (125–15.6 µg/mL) were pre-incubated with 5000 plaque-forming units (PFU) of SARS-CoV-2 for one hour. Subsequently, mixtures were added to human Calu-3 cells and incubated for 24 h. After incubation with a SARS-CoV-2 N-specific primary antibody and peroxidase-labelled secondary antibody, the enzyme reaction was visualized by adding tetramethylbenzidine. Absorbance was measured with a microplate multireader at OD450. Statistical analysis was performed with one-way analysis of variance (ANOVA) and Dunnett’s multiple comparison test using GraphPad Prism. ** p < 0.01; *** p < 0.001; and **** p < 0.0001; error bars represent the standard error of the mean (SEM). NC = negative control (medium); PC = positive control (5000 PFU SARS-CoV-2). (B) The cytotoxic effect of various concentrations of aqueous turmeric root extract, nutritional supplement capsule, and curcumin toward Calu-3 cells was determined by Orangu™ Cell Counting Solution (Cell guidance systems) after 24 h. The cell viability was normalized to untreated control cells. Error bars represent the SEM.

In order to determine the dose-dependent antiviral activity, the study team determined the EC50 of turmeric root extract was achieved at a dilution of 1:63.5.
 
Comparatively, the EC50 values of the capsules and curcumin were achieved at a concentration of 7.4 micrograms (µg)/mL and 7.9 µg/mL, respectively. No cytotoxic effect was observed.
 
As a result that the potential antiviral compounds against SARS-CoV-2 may present an antiviral effect that can be cell-line dependent, the study team demonstrated efficient curcumin-mediated inhibition of SARS-CoV-2 infection in both cell lines, thereby indicating a genuine antiviral effect of curcumin against SARS-CoV-2.
 
Importantly the antiviral activity of a human cell line assessed by an in-cell ELISA (icELISA)-based neutralization test (icNT) showed all tested mixtures potently neutralized SARS-CoV-2 at subtoxic concentrations. They found that low concentrations of 58.6 µg/mL of the dissolved supplement capsules, 15.6 µg/mL of curcumin, and a high dilution of 1:128 of turmeric root extract were sufficient to significantly neutralize SARS-CoV-2.
 
The study findings significantly demonstrated for the first time a potent antiviral activity of turmeric root and its bioactive ingredient curcumin against SARS-CoV-2 on Vero-E6 and Calu-3 cells.
 
The study team further performed a dose-dependent activity of curcumin on the SARS-CoV-2 RNA genome copy numbers and found an EC50 of about 14 µg/mL (about 38 µM). The results correlated well with the above-mentioned observations of neutralization efficacy.
 
On the issue of the possible mechanisms of action of curcumin against SARS-CoV-2, the study team suggested the inhibition of viral entry into the host cell. As indicated in previous in silico studies, the keto and enol forms of curcumin H-bonds strongly bind with the viral spike protein and the host angiotensin-converting enzyme 2 (ACE2) receptor. https://www.nature.com/articles/s41598-021-81462-7
 
Although the issue of its low bioavailability and aqueous solubility presents a limitation, the results from this study highlight curcumin as a potent antiviral compound at low concentrations against SARS-CoV-2.
 
The study findings demonstrated that the aqueous turmeric root extract, dissolved nutritional supplement capsules, as well as curcumin alone efficiently neutralized SARS-CoV-2 in Vero E6 and Calu-3 cell culture models.
 
Although results from undergoing clinical studies on the evaluation of benefits of curcumin the treatment of COVID-19 patients are pending, this study strongly demonstrates its activity against SARS-CoV-2 in vitro. The results discussed here to reaffirm that herbal medicines, which are cost-effective and easily available across the world, with antiviral activity are promising candidates for the complementary treatment of viral infections such as SARS-CoV-2 infections.
 
Readers should however be wary when procuring curcumin products including supplements or even combined herbal therapeutic compounds containing curcumin. As far as possible stay away from products made in India due to high incidence of adulteration and contamination even from so called GMP certified manufacturers. https://www.thailandmedical.news/news/80-percent-of-curcumin-supplies-and-supplements-contaminated-by-lead
 
Also be wary of certain so-called new biotech firms flogging so called COVID-19 therapeutic products that are made in India and some that contain extremely low doses of the necessary phytochemicals and are worse than placebo homeopathic suspensions.
 
For more on COVID-19 Herbs, keep on logging to Thailand Medical News.