by Two common wild plants contain extracts that inhibit the virus that causes COVID-19’s ability to infect living cells, according to a new study.
The study, published in Scientific Reportsis the first major screening of plant extracts to look for efficacy against the SARS-CoV-2 virus, the researchers say.
In laboratory dish tests, extracts from the flowers of the goldenrod (Solidago altissima) and the rhizomes of bracken (Pteridium aquilinum) each blocked the entry of SARS-CoV-2 into human cells.
The active ingredients are only present in the plants in minimal amounts. It would be ineffective and potentially dangerous if people tried to treat themselves, the researchers point out. In fact, bracken is known to be poisonous, they warn.
“It’s still very early in the process, but we’re working to identify, isolate, and scale up the molecules from the extracts that showed activity against the virus,” says senior author Cassandra Quave, associate professor in Emory’s Department of Dermatology School of Medicine and the Center for the Study of Human Health. “Once we have isolated the compounds, we plan to conduct further testing for their safety and long-term potential as drugs against COVID-19.”
Medicinal products from plants and fungi
Quave is an ethnobotanist, studying how traditional people used plants for medicine to identify promising new candidates for modern medicines. Her lab curates the Quave Natural Product Library, which contains thousands of botanical and fungal natural products derived from plants collected from locations around the world.
Caitlin Risener, a graduate student in Emory’s Molecular and Systems Pharmacology Graduate Program and at the Center for the Study of Human Health, is the lead author of the current publication.
In previous research to identify potential molecules to treat drug-resistant bacterial infections, the Quave lab focused on plants that traditional people had used to treat skin inflammation.
Because COVID-19 is an emerging disease, researchers took a broader approach. They developed a method to quickly test more than 1,800 extracts and 18 compounds from the Quave Natural Product Library for activity against SARS-CoV-2.
“We have shown that our library of natural products is a powerful tool to help find potential therapeutics for an emerging disease,” says Risener. “Other researchers can adapt our screening method to look for other novel compounds in plants and fungi that could lead to new drugs to treat a range of pathogens.”
Plants provide COVID protection
SARS-CoV-2 is an RNA virus with a spike protein that can bind to a protein called ACE2 on host cells. “The viral spike protein uses the ACE2 protein almost like a key that is put in a lock to allow the virus to enter and infect a cell,” explains Quave.
Researchers designed experiments using SARS-CoV-2 virus-like particles, or VLPs, and cells programmed to overexpress ACE2 on their surface. VLPs have been stripped of the genetic information needed to cause COVID-19 infection. Instead, when a VLP managed to bind to an ACE2 protein and enter a cell, it was programmed to hijack the cell’s machinery to activate a fluorescent green protein.
The researchers added a plant extract to the cells in a petri dish before introducing the virus particles. By shining a fluorescent light on the dish, they were able to quickly determine whether the virus particles had managed to enter the cells and activate the green protein.
The researchers identified a handful of hits for extracts that protected against virus entry, then focused on those that showed the strongest activity: Tall goldenrod and bracken. Both types of plants are native to North America and are known for their traditional medicinal uses by Native Americans.
Additional experiments showed that the protective power of the plant extracts worked across four variants of SARS-CoV-2: alpha, theta, delta and gamma.
Plants for infectious diseases
To further test these results, the Quave lab worked with co-author Raymond Schinazi, professor of pediatrics, director of Emory’s Division of Laboratory of Biochemical Pharmacology, and co-director of the HIV Cure Scientific Working Group within the NIH-sponsored Emory University Center for AIDS together research. A global leader in antiviral development, Schinazi is best known for his pioneering work on breakthrough HIV drugs.
The Schinazi lab’s higher biosafety rating allowed the researchers to test the two plant extracts in experiments with the infectious SARS-CoV-2 virus instead of VLPs. The results confirmed the ability of goldenrod and bracken extracts to inhibit the ability of SARS-CoV-2 to attach to and infect a living cell.
“Our results set the stage for future use of natural product libraries to find new tools or therapies against infectious diseases,” says Quave.
As a next step, the researchers are working to determine the exact mechanism that allows the two plant extracts to block binding to ACE2 proteins.
Medical potential
For Risener, one of the best parts of the project is that she collected samples of large goldenrod and bracken herself. In addition to collecting medicinal plants from around the world, the Quave lab also takes field trips to the forests of the Joseph W. Jones Research Center in South Georgia. The Woodruff Foundation established the center to conserve one of the last remnants of the unique scots pine ecosystem that once dominated the southeastern United States.
“It’s great to go out into nature to identify and dig up plants,” says Risener. “It’s something that very few PhD pharmacology students can do. I will be covered in dirt from head to toe, kneeling on the floor and beaming with excitement and happiness.”
She also assists in preparing the plant extracts and assembling the specimens for the Emory herbarium. “When you collect a sample yourself and dry and preserve the samples, that creates a personal connection,” she says. “It’s different than when someone in a lab just hands you a vial of plant material and says, ‘Analyze that.'”
After graduating, Risener aspires to a career in public relations and science policy education related to natural product research. Some of the better-known medicinal products derived from plants include aspirin (from willow), penicillin (from mushrooms), and the cancer drug taxol (from yew trees).
“Plants are so chemically complex that humans probably couldn’t think of all the botanical compounds waiting to be discovered,” says Risener. “The enormous medicinal potential of plants underscores the importance of preserving ecosystems.”
Additional co-authors are from Missouri Botanical Gardens and Emory. The Marcus Foundation, the Center for AIDS Research, and the National Center for Complementary and Integrative Health funded the work.
Source: Emory University
