Extract of medicinal plant Artemisia annua interferes with replication of SARS-CoV-2 in vitro

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trader32176
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Extract of medicinal plant Artemisia annua interferes with replication of SARS-CoV-2 in vitro

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Extract of medicinal plant Artemisia annua interferes with replication of SARS-CoV-2 in vitro

1/11/21

https://www.news-medical.net/news/20210 ... vitro.aspx


Researchers in the United States have shown that extracts of an aromatic herb called Artemisia annua inhibit the replication of severe acute respiratory coronavirus (SARS-CoV-2) – the agent responsible for the current coronavirus disease 2019 (COVID-19) pandemic.

Also known as “Sweet wormwood,” Artemisia annua (A. annua) is an herb from Asia that produces the antimalarial agent artemisinin.

Now, researchers at Columbia University in New York, the University of Washington, and Worcester Polytechnic Institute have demonstrated that hot-water leaf A. annua extracts based on artemisinin, total flavonoids, or dry leaf mass show antiviral activity against SARS-CoV-2.

“This is the first report of anti-SARS-CoV-2 efficacy of hot water extracts of a wide variety of cultivars of A. annua sourced from four continents,” says Pamela Weathers and colleagues. “Further studies will determine in vivo efficacy to assess whether A. annua might provide a cost-effective therapeutic to treat SARS-CoV-2 infections.”

A pre-print version of the paper is available on the bioRxiv* server, while the article undergoes peer review.

Antiviral activity of the herb has been shown before


The medicinal plant A. annua and the artemisinin it produces have been safely used to treat a range of ailments, particularly malaria, for more than 2,000 years.

One study conducted in 2005 also demonstrated that the herb has an antiviral effect against SARS-CoV-1 – the agent responsible for the 2002 to 2003 SARS outbreak.

Furthermore, both the A. annua plant and artemisinin have been shown to reduce levels of the inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in vivo.

“These effector molecules can be problematic during the ‘cytokine storm’ suffered by many SARS-CoV-2 patients,” says Weathers and the team.

What did the current study involve?

The team hypothesized that encapsulated powdered dried leaves of A. annua might represent a safe and cost-effective approach to treating SARS-CoV- 2 infections.

The researchers tested the effects of extracts from seven A. annua cultivars sourced from four different continents on SARS-CoV-2 propagated in Vero E6 cells. They also assessed correlations of antiviral efficacy with artemisinin, total flavonoid contents, and dry leaf mass.

All extracts demonstrated anti-SARS-CoV-2 activity. The IC50 values (concentration of drug that inhibits 50% of target) calculated based on artemisinin, total flavonoid content or dry leaf mass ranged from 0.1 to 8.7µM, 0.01 to 0.14µg and 23.4-57.4µg, respectively.

One sample that was obtained in 2008 still exhibited anti-SARS-CoV-2 activity that was comparable to the most recently harvested cultivar samples.

This suggests that the active principle is ubiquitous to different A. annua cultivars and is chemically stable during long-term room temperature dry storage, say the researchers.

Antiviral efficacy was inversely correlated with artemisinin and total flavonoid contents

Although the hot water extracts were effective, antiviral efficacy was inversely correlated with artemisinin and total flavonoid contents.

Analysis of artemisinin alone had an estimated IC50 of around 70µM, and while the artemisinin derivative artemether showed efficacy at 1.23µM, it was cytotoxic at concentrations any higher than this.

The derivatives artesunate and dihydroartemisinin were also ineffective at levels of less than 100µM.

By contrast, the antimalarial drug amodiaquine had an IC50 of 5.8 µM.

Furthermore, Spearman’s Rho analysis showed that neither IC50 nor IC90 values of the hot-water extracts correlated with artemisinin or total flavonoid content.

The researchers also found that the extracts had minimal antiviral effects against pseudoviruses containing the SARS-CoV-2 spike protein – the main structure the virus uses to bind to and enter host cells. The team says this suggests that A. annua inhibits SARS-CoV 2 infection primarily by targeting a post-entry step.

“The results suggest the active component in the extracts is likely something besides artemisinin or is a combination of components acting synergistically to block post-entry viral infection,” says Weathers and colleagues.

Investigating the effects of dried leaf A. annua consumption

To investigate dried leaf A. annua (DLA) as a potential therapeutic, Weathers consumed 3 grams of encapsulated DLA of the SAM cultivar, and the team tracked artemisinin as a marker molecule by drawing blood samples two and five hours later.

At two and five hours following ingestion, the artemisinin levels were 7.04µg and 0.16 µg per mL serum, respectively. At 2 hours, this corresponded to 2.35µg artemisinin/mL serum of DLA-delivered artemisinin per gram of DLA consumed.

The researchers say that while human trials are clearly needed, the study suggests that consuming reasonable amounts of DLA may serve as a cost-effective treatment for SARS-CoV-2 infection.


“If subsequent clinical trials are successful, A. annua could potentially serve as a safe therapeutic that could be provided globally at a reasonable cost and offer an alternative to vaccines,” concludes the team.

*Important Notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:

Weathers P, et al. Artemisia annua L. extracts prevent in vitro replication of SARS-CoV-2. bioRxiv, 2020. doi: https://doi.org/10.1101/2021.01.08.425825, https://www.biorxiv.org/content/10.1101 ... 8.425825v1
trader32176
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Re: Extract of medicinal plant Artemisia annua interferes with replication of SARS-CoV-2 in vitro

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Artemisia plant extracts show potential anti-SARS-CoV-2 activity in vitro

2/16/21


https://www.news-medical.net/news/20210 ... vitro.aspx


A team of scientists from Germany and the USA recently explored the effectiveness of traditional plant medicines in treating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Their findings reveal that various extracts of two medicinal plants, namely Artemisia annua and Artemisia afra, can potentially inhibit SARS-CoV-2 replication in vitro without causing any cytotoxicity. The study is currently available on the bioRxiv* preprint server.

Background

The recent outbreak of coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 pathogen, has put a large burden on the healthcare systems of many countries globally. Although about 80% of COVID-19 patients develop only mild symptoms or remain asymptomatic, the disease has claimed more than 2.4 million lives worldwide since its emergence in December 2019. In the initial phase of the pandemic, many antiviral medicines already approved for other diseases have been repurposed to treat critically ill COVID-19 patients. Many vaccines with good efficacy and safety levels have also been developed and approved in record time to curb the pandemic's growth.

Various synthetic derivatives (artesunate) of artemisinin, which is a bioactive natural compound found in Artemisia annua plants, are typically being used as antimalarial medicines. The antimicrobial properties of these bioactive compounds have been recognized clinically. Different extracts of Artemisia annua containing high amount of artemisinin are currently undergoing phase 2 clinical trials to treat COVID-19 patients. Since April 2020 in Madagascar, Covid-Organics drinks containing mainly Artemisia annua extracts are being used as a miracle intervention to treat and prevent COVID-19.

In the current study, the scientists have explored the efficacy of Artemisia annua and Artemisia afra extracts and Covid-Organics in preventing SARS-CoV-2 infection in vitro. Using various animal cell lines, they specifically examined whether these plant products are able to inhibit replication of SARS-CoV-2 and feline coronavirus.

Important observations


Both water and ethanolic extracts of dried leaves of Artemisia annua and Artemisia afra were used in this study. In addition, 500 mg of pure artemisinin and dried form of 50 ml of Covid-Organics were dissolved in dimethyl sulfoxide and tested for activity using various in vitro experimentations.

To determine its antiviral activity, the scientists first incubated feline coronavirus with different concentrations of plant extracts and pure artemisinin solution on a monolayer of feline kidney cells. Using plaque formation assay, they observed that all tested extracts significantly inhibited viral replication in a dose-dependent manner. Specifically, they observed that at a concentration range of 5 – 10 mg/ml, all tested extracts significantly inhibited viral replication, whereas no inhibition was observed at less than 2 mg/ml concentration. Based on these findings, they selected the most potent extracts with the highest antiviral activity for further experimentations on SARS-CoV-2.

A set of experiments conducted using the monkey kidney cell line revealed that the extracts at a concentration of less than 2 mg/ml had potent antiviral activity against SARS-CoV-2. The strongest SARS-CoV-2 inhibitory effects were observed for water extracts of Artemisia annua and Artemisia afra and an ethanolic extract of Artemisia annua. Since Artemisia afra does not contain artemisinin, the scientists believe that other bioactive compounds present in the plant may be responsible for the observed anti-SARS-CoV-2 activity.

Using a separate set of experiments, the scientists estimated that these extracts could induce cytotoxic effects at a concentration range of 10 – 20 mg/ml, which was significantly higher than the concentrations required for antiviral activities. This observation indicates that these extracts can potently inhibit SARS-CoV-2 replication without affecting cell viability.

The preparations made from Covid-Organics drink showed higher antiviral activity against SARS-CoV-2 compared to Feline coronavirus. However, the selectivity index (the window between cytotoxicity and antiviral activity) of Covid-Organics drink was estimated to be 5.2, making it less promising as an antiviral medicine.

Study significance

The study reveals that various extracts of Artemisia annua and Artemisia afra have potential antiviral activities against SARS-CoV-2. However, the scientists mention that further studies are required to check whether appropriate serum levels of Artemisia compounds needed to inhibit SARS-CoV-2 can be achieved in patients. Moreover, further animal and human clinical trials are required to determine whether these in vitro observations can be translated for actual clinical use.

*Important Notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:

Chuanxiong Nie, Jakob Trimpert, Sooyeon Moon, Rainer Haag, Kerry Gilmore, Benedikt B. Kaufer, Peter H. Seeberger. 2021. In vitro efficacy of Artemisia extracts against SARS-CoV-2. BioRxiv. doi: https://doi.org/10.1101/2021.02.14.431122, https://www.biorxiv.org/content/10.1101 ... 4.431122v1
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