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

Xinyu Qi; Binglin Li; Alejandra B Omarini; Martin Gand; Xiaoli Zhang; Jiao Wang

doi:10.1016/j.molstruc.2022.133709

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

J Mol Struct. 2022 Nov 15:1268:133709. doi: 10.1016/j.molstruc.2022.133709. Epub 2022 Jul 12.

Authors

Xinyu Qi¹, Binglin Li¹, Alejandra B Omarini², Martin Gand³, Xiaoli Zhang¹, Jiao Wang^{1

4

5}

Affiliations

¹ College of Food Science and Engineering, Northwest University, 229 North Taibai Road, Xi'an, 710000, Shaanxi, China.
² Institute of Earth and Environmental Sciences of La Pampa, Universidad Nacional de La Pampa, Mendoza 109, L6300DUG, Santa Rosa, La Pampa, Argentina.
³ Institute of Food Chemistry and Food Biotechnology, Justus Liebig University, Giessen, Germany, Heinrich-Buff-Ring 17, Giessen, 35392 Germany.
⁴ BioQuant, Heidelberg University, Heidelberg 69120, Germany.
⁵ Biochemistry Center (BZH), Heidelberg University, Heidelberg 69120, Germany.

Abstract

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 (M^pro) of SARS‑CoV‑2 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 M^pro of SARS‑CoV‑2. 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%.

Keywords: Main protease (Mpro); Molecular docking; SARS‑CoV‑2; Screening; TCM.