In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus

Abstract

Objective: In this study we execute a rational screen to identify Chinese medical herbs that are commonly used in treating viral respiratory infections and also contain compounds that might directly inhibit 2019 novel coronavirus (2019-nCoV), an ongoing novel coronavirus that causes pneumonia.

Methods: There were two main steps in the screening process. In the first step we conducted a literature search for natural compounds that had been biologically confirmed as against sever acute respiratory syndrome coronavirus or Middle East respiratory syndrome coronavirus. Resulting compounds were cross-checked for listing in the Traditional Chinese Medicine Systems Pharmacology Database. Compounds meeting both requirements were subjected to absorption, distribution, metabolism and excretion (ADME) evaluation to verify that oral administration would be effective. Next, a docking analysis was used to test whether the compound had the potential for direct 2019-nCoV protein interaction. In the second step we searched Chinese herbal databases to identify plants containing the selected compounds. Plants containing 2 or more of the compounds identified in our screen were then checked against the catalogue for classic herbal usage. Finally, network pharmacology analysis was used to predict the general in vivo effects of each selected herb.

Results: Of the natural compounds screened, 13 that exist in traditional Chinese medicines were also found to have potential anti-2019-nCoV activity. Further, 125 Chinese herbs were found to contain 2 or more of these 13 compounds. Of these 125 herbs, 26 are classically catalogued as treating viral respiratory infections. Network pharmacology analysis predicted that the general in vivo roles of these 26 herbal plants were related to regulating viral infection, immune/inflammation reactions and hypoxia response.

Conclusion: Chinese herbal treatments classically used for treating viral respiratory infection might contain direct anti-2019-nCoV compounds.

Keywords: 2019-nCoV; Chinese herbal; Drugs; Molecular docking; Natural compounds; Network pharmacology; Pneumonia; Wuhan coronavirus.

Fig. 1

Workflow scheme. The work is divided into two main parts, natural compound selection and herbal plant selection. Each part consists of three steps. As detailed in the text, oral effectiveness is important in compound selection, while in the plant selection portion, the selected herbs should be compatible with the classic usages of herbal treatment in traditional Chinese medicine. TCMSP: Traditional Chinese Medicine Systems Pharmacology.

Fig. 2

Docking between selected natural compounds and their reported targets. A. PLpro and natural compound M2; B. 3CL and M1; C. Spike and M6. Docking is performed with AutoDock 4 which is detailed in Materials and Methods. The protein structure files are listed in Table 1. Protein domains are shown in different colors, while natural compounds are shown in dark yellow. The amino acids labeled were those interacting with compound. 3CLpro: 3C-like protease; PLpro: papain-like protease.

Fig. 3

Kyoto Encyclopedia of Genes and Genomes pathways enriched for the herb Forsythiae Fructus in network pharmacology analysis. The top 30 pathways are shown. The blue, red and green bars represent the pathways related to viral infection, immune/inflammation response, and hypoxia response, respectively. EGFR: epidermal growth factor receptor; AGE: advanced glycation end product; RAGE: receptor for AGE.