Summary: Researchers are investigating the medicinal properties of Artemisia annua, commonly called Sweet Annie, focusing on a compound named arteannuin B. Their interdisciplinary study explores how this molecule exerts bioactive effects against glioblastoma brain cancer cells and the SARS-CoV-2 virus that causes COVID-19.
An integrated team of biologists, chemists and neuropharmacologists at UTSA have begun to define the mechanism behind Sweet Annie’s activity. Their laboratory work isolates leaf extracts, separates chemical fractions, and tests these components for cytotoxic and antiviral effects, identifying arteannuin B as a consistently active molecule against malignant brain tumor cells.
Key Facts:
- Artemisia annua (Sweet Annie) has a long history in traditional Chinese medicine and produces artemisinin; its leaf extracts also contain other biologically active compounds under investigation for cancer and antiviral uses.
- UTSA researchers are among the first to demonstrate how one molecule from Sweet Annie—arteannuin B—interacts with target proteins, using complementary approaches from chemistry, biochemistry and cell biology.
- Laboratory results indicate arteannuin B shows repeatable cytotoxicity against glioblastoma cells and appears to inhibit cysteine proteases, a class of protein-cleaving enzymes often overexpressed in cancer and required for viral replication.
Source: UT San Antonio
Vibrant green leaves rise from tall, fragrant Artemisia annua plants growing in terracotta pots inside UTSA laboratories. In one lab, leaves are harvested and extracted; in another, the resulting fractions are chemically characterized; and in cell culture facilities, these compounds are tested for effects on cancer cells.
Artemisia annua contains multiple bioactive molecules. UTSA investigators are concentrating on arteannuin B to determine how it interacts with cellular targets in glioblastoma (GBM) and with viral proteins associated with SARS-CoV-2. Their goal is to understand the underlying chemistry and biology so that any therapeutic potential can be guided by mechanistic insight.
“About half of prescription medicines have origins in natural products produced by plants, fungi, or bacteria,” said Valerie Sponsel. “Different plants synthesize different chemical scaffolds. For complex diseases such as cancer, no single compound will treat all forms, so discovering and characterizing new molecules remains essential.”
Artemisia annua is best known for producing artemisinin, which transformed malaria treatment. Historically, leaf extracts have also been used in various contexts, including experimental applications against cancer and COVID-19. Contemporary clinical interest ranges from preparations infused into beverages to more controlled laboratory evaluations.
Until now, the precise molecular mechanisms of many A. annua extract components were unclear. UTSA researchers—Valerie Sponsel, Francis Yoshimoto and Annie Lin—combined expertise in plant biology, organic chemistry and neurobiology to map how arteannuin B reacts with biological targets and to link that chemistry to observed antiviral and cytotoxic effects.
The team used methanol-based solvents to extract leaf material, then fractionated the extracts by liquid chromatography and characterized components using NMR spectroscopy and mass spectrometry. Fractions were screened for cytotoxicity against primary glioblastoma cells supplied by collaborators at UCSF.
Arteannuin B repeatedly showed cytotoxic activity in GBM assays. Chemical modification experiments revealed that reducing arteannuin B abolished its activity at comparable concentrations, a key clue that the compound’s specific chemical features are required for its bioactivity. Additional enzymatic assays revealed that arteannuin B can inhibit cysteine proteases—enzymes that use an active-site cysteine residue to cleave peptide bonds—suggesting a common mechanism across targets.
Further biochemical work demonstrated time-dependent inhibition of the SARS-CoV-2 main protease (NSP5), a cysteine protease, and mass spectrometry provided evidence of covalent adduction to the enzyme’s active-site cysteine. Parallel experiments with caspase-8, a cysteine protease implicated in glioblastoma biology, showed similar time-dependent inhibition and covalent modification of the active-site cysteine. These observations support a thiol–Michael addition mechanism in which the electrophilic features of arteannuin B react with nucleophilic cysteine residues on target proteins.
Understanding this mechanism is important for translating natural-product discoveries into targeted therapeutics. As Francis Yoshimoto noted, knowing how a compound becomes active and which proteins it modifies enables rational strategies to deliver the compound, control dosing, and design derivatives with improved specificity and safety. Personalized factors — such as variable expression of metabolizing enzymes in patients — influence drug effectiveness, and mechanistic insight helps anticipate and address such variability.
The study represents a collaborative effort, with clinical-grade glioblastoma samples and expertise contributed by Mitchel S. Berger and the UCSF Brain Tumor Center. The findings were detailed in a peer-reviewed report that links a clear chemical reaction to antiviral and anticancer activities and outlines a plausible biochemical basis for arteannuin B’s bioactivity.
About this brain cancer and neuropharmacology research news
Author: Andrea Ari Castaneda
Source: UT San Antonio
Contact: Andrea Ari Castaneda – UT San Antonio
Image: The image is credited to Neuroscience News
Original Research: Open access. “Inhibition of Cysteine Proteases via Thiol-Michael Addition Explains the Anti-SARS-CoV-2 and Bioactive Properties of Arteannuin B” by Valerie Sponsel et al., Journal of Natural Products. The study reports isolation of arteannuin B derivatives from A. annua extracts, chemical and spectroscopic characterization, and biochemical assays demonstrating covalent cysteine modification and time-dependent inhibition of target proteases.
Abstract
Inhibition of Cysteine Proteases via Thiol-Michael Addition Explains the Anti-SARS-CoV-2 and Bioactive Properties of Arteannuin B
Artemisia annua produces artemisinin and other sesquiterpenoids. Extracts from A. annua include arteannuin B and related compounds that have been investigated for antiviral and anticancer activities. In controlled extractions with methanol and dichloromethane, a methyl ester derivative of arteannuin B was observed, consistent with solvent-mediated addition reactions. Experiments with thiol reagents demonstrated 1,4-addition (a thiol–Michael reaction) under appropriate conditions.
Biochemical assays showed arteannuin B inhibits the SARS-CoV-2 main protease (NSP5) in a time-dependent manner, and mass spectrometry indicated covalent bond formation with the active-site cysteine residue. Complementary assays with caspase-8, a cysteine protease relevant to glioblastoma, produced comparable results: time-dependent inhibition and evidence of cysteine adduction at the enzyme’s active site. Collectively, these findings provide a mechanistic explanation for certain antiviral and cytotoxic properties of A. annua extracts and identify arteannuin B as a bioactive scaffold worthy of further investigation.