Discovery of TCMs and derivatives against the main protease of SARS-CoV-2 via high throughput screening, ADMET analysis, and inhibition assay in vitro.

The rapidly evolving Coronavirus Disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide with thousands of deaths and infected cases. For the identification of effective treatments against this disease, the main protease (Mpro) of SARS­CoV­2 was found to be an attractive drug target, as it played a central role in viral replication and transcription. Here, we report the results of high-throughput molecular docking with 1,045,468 ligands' structures from 116 kinds of traditional Chinese medicine (TCM). Subsequently, 465 promising candidates were obtained, showing high binding affinities. The dynamic simulation, ADMET (absorption, distribution, metabolism, excretion and toxicity) and drug-likeness properties were further analyzed the screened docking results. Basing on these simulation results, 23 kinds of Chinese herbal extracts were employed to study their inhibitory activity for Mpro of SARS­CoV­2. Plants extracts from Forsythiae Fructus, Radix Puerariae, Radix astragali, Anemarrhenae Rhizoma showed acceptable inhibitory efficiencies, which were over 70%. The best candidate was Anemarrhenae Rhizoma, reaching 78.9%.

Virtual screening for functional foods against the main protease of SARS-CoV-2.

The special attention was paid on the interaction between functional foods and the main protease of severe acute respiratory syndrome coronavirus (SARS-CoV-2). Here, 10,870 ligands were employed and screened by the molecular docking, which involved 12 kinds of functional foods (carbohydrates, fatty acids, phospholipids, vitamin, ß-sitosterol, flavonoids, nordihydroguaiaretic acid, curcumin, nootkatone, ß-pinene, tincturoid, betulinic acid, and their isomers/analogs/derivatives). Then, 60 ligands were obtained with the good docking affinity. Most of them belong to quercetrin and its isomers/analogs/derivatives, which also showed the highest affinity for the main protease of SARS-CoV-2. The dynamic simulation indicated that quercetrin-protease and quercetrin-analog-protease showed the excellent stability. Compared with reported docking results, quercetrin should be the best inhibitor for the main protease of SARS-CoV-2. Considering the green and white tea are rich in quercetrin and its isomers/analogs/derivatives, tea and relative beverages may become a good option to regulate our metabolism and help us to overcome this special time. PRACTICAL APPLICATIONS: The docking and molecular dynamics technology were combined to screen the functional foods, which would be the potential candidate of the inhibitor for SARS-CoV-2. Many functional foods screened in this work belong to necessary nutrients for body. Thus, SARS-CoV-2 would consume some necessary nutrients, and thus, damage our body. It should be further consideration whether exogenous nutrients should be provided to slow, halt, or reverse biochemical alterations and structural deterioration in our body. On the contrary, this work also provided a new possibility to design a functional food or drug to help us overcome this special time.