Phytochemical Discrimination, Biological Activity and Molecular Docking of Water-Soluble Inhibitors from Saussurea costus Herb against Main Protease of SARS-CoV-2

A 10,000-year-old herbal remedy may hold new secrets against COVID-19—and this time, it's all about water.

Siddha medicine, one of the world's oldest healing traditions, has been quietly practicing for over 10,000 years. Now, scientists have turned to its botanical arsenal, specifically Saussurea costus, to hunt for water-soluble inhibitors against the main protease of SARS-CoV-2. Why water-soluble? Because compounds that dissolve easily in water are more bioavailable and simpler for the body to eliminate—a practical advantage in drug design.

Using a green extraction method with room-temperature water, researchers identified 48 compounds via GC-MS. Fatty acids dominated the profile at 73.8%, followed by tannins (8.2%), carbohydrates (6.9%), and a smattering of terpenoids, carboxylic acids, and others. Of these, 22 compounds were docked against the active site of Mpro, focusing on the catalytic dyad His41 and Cys145. The best binders—4,8,13-Cyclotetradecatriene-1,3-diol, Andrographolide, and delta.4-Androstene-3.beta.,17.beta.-diol—showed binding affinities from −6.1 to −6.5 kcal/mol.

But the story doesn't end at docking. In pseudovirus assays, the aqueous extract did not block viral entry, nor did it kill the virus directly; instead, it inhibited SARS-CoV-2 after cell entry. The extract also showed activity against HSV-1 and two bacterial strains, Staphylococcus aureus and Escherichia coli. This unprecedented haul of water-soluble Mpro inhibitors from Saussurea costus opens a promising, eco-friendly avenue for antiviral drug development.

Key Points

• 48 compounds identified in water extract via GC-MS
• Best Mpro inhibitors bind −6.1 to −6.5 kcal/mol
• Extract blocks SARS-CoV-2 after cell entry, not virucidal