Coronavirus type 2 of severe acute respiratory syndrome (SARS-cov-2) causes coronavirus disease (COVID-19) in humans and there is no cure. In the fight against COVID-19 epidemic, traditional Chinese medicine (TCM) has once again attracted attention, and caused widespread concern in the world. In the exchange and practice of China and other countries to fight against the epidemic, TCM is known in many countries for its efficacy.
Recently, the research achievements and progress on TCM have also been promoted. Especially in the Chinese medicine of baicalin, the latest findings are: baicalin and baicalein can effectively inhibit the new coronavirus. In January this year, the Cancer Hospital of the Chinese Academy of Medical Sciences and Yale University of the United States collaborated to study the efficacy of scutellaria decoction in cancer treatment. The 3c protease (3CLpro) is a highly conserved protease that is essential in the process of coronavirus replication and is a promising target for the development of broad-spectrum antiviral drugs.
In order to speed up drug discovery and development, researchers from the Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China University of Pharmaceutical Sciences, Shanghai University of Science and Technology and other units have studied the inhibitory effect of natural products from traditional Chinese medicine on SARS-CoV-2 3CLpro. The results were published online on April 15 on the bioprinter platform bioRxiv. The paper titled “Discovery of baicalin and baicalein as novel, natural product inhibitors of SARS-CoV-2 3CL protease in vitro”.
The researchers discovered for the first time non-covalent, non-peptide SARS-CoV-2 3CLpro inhibitors-baicalin and baicalein. The researchers found in the cell experiment that these two components showed strong antiviral activity in the cell system. Baicalin is a flavonoid compound isolated from the dried roots of Scutellaria baicalensis Georgi. Baicalein is mainly present in Scutellaria baicalensis, and it is one of the flavonoids with the highest content in Scutellaria baicalensis. Baicalein has anti-inflammatory, anti-allergic, diuretic, choleretic, cholesterol lowering, anti-thrombotic, and asthma-relieving effects.
In order to evaluate the antiviral activity and biosafety of baicalin and baicalein in detail, Vero E6 of sars-cov-2 infected African green monkey kidney cell line and Vero E6 of normal African green monkey kidney cell line were selected as experimental subjects. In the experiment, baicalin and baicalein only need a small dose to significantly inhibit the new coronavirus. The half maximum effect concentrations of the two compounds were 10.27 and 1.69 μM, respectively. The experimental results show that the antiviral activities of the two are superior to other compounds. And the cytotoxic concentration (CC50) of these two compounds exceeds 200 μM, which shows that the side effects of the two traditional Chinese medicine ingredients are extremely low.
Scutellaria can inhibit the new coronavirus mainly because all the two compounds it contains can effectively inhibit the replication of an important protease 3CLpro in the new coronavirus. Baicalin and baicalein were identified as the first non-covalent, non-polypeptide SARS-CoV-2 3CLpro inhibitors.
It is worth noting that the combination of baicalein with SARS-CoV-2 3CLpro determined by x-ray protein crystallography is significantly different from known inhibitors. By interacting with two catalytic residues (the key S1/S2 subsite and the oxygen anion ring), baicalin is perfectly anchored to the center of the substrate binding site, acting as a “shield” in front of the catalytic binary, preventing the peptide substrate from approaching the active site.
Baicalein can bind to protease residues Leu141 / Gly141 / Ser144 through a series of direct and indirect hydrogen bonds to fix the free oxygen anion ring structure to stabilize the tetrahedral transition state in the proteolytic reaction. A series of results comprehensively show the details of baicalein’s recognition of SARS-CoV-2 3 CLpro at the molecular level, and explain the possible reasons that baicalein can significantly inhibit the activity of SARS-CoV-2 3 CLpro.
In general, baicalin’s simple chemical structure, unique mode of action, and strong in vitro antiviral activity, coupled with good safety data from clinical trials, offer a great opportunity to develop baicalin as an urgently needed anti-coronavirus drug.
- Haixia Su et al. Discovery of baicalin and baicalein as novel, natural product inhibitors of SARS-CoV-2 3CL protease in vitro. bioRxiv. 2020. Doi:https：//doi.org/10.1101/2020.04.13.038687