Research On Intervention of New Coronavirus (SARS-CoV-2) Based on Molecular Docking Technology on Mongolian Medicine Active Components

Abstract Objective This article intends to use molecular docking technology to find potential inhibitors that can cope with new coronaviruses from the active compounds of Mongolian drug Nagebu-9. Methods The TAGSP, ETCM database and literature mining methods were used to collect the active compounds of Nagebu-9; the Swiss Target Prediction and SUPERPRED servers were used to find the target of the compound. At the same time, Drugbank and Genecard databases were used to collect antiviral drug targets. The above targets were compared and analyzed, and the antiviral targets of Nagebu-9 were selected. The Metascape database platform was used to perform GO (Gene ontology) annotation and KEGG pathway enrichment analysis on the target. In view of the high homology between the RCD domain of the new coronavirus S-protein and the SARS virus gene sequence, as well as the similarity in the pathogenic mechanism and clinical manifestation of the two diseases. We used the Swiss-Model to establish a new coronavirus S protein model, use the ZDOCK protein docking software to dock the S protein with the human angiotensin ACE2 protein to find the key amino acids at the binding site. Using ACE2 as the receptor, AutoDock molecular docking software was used to conduct molecular docking studies on the active ingredients and the target protein. The interaction between the ligand and the receptor are used to provide options for screening anti-coronavirus drugs. Results A total of 262 active ingredients were screened from the nine ingredients of Mongolian medicine Nagebu-9, and through Metascape analysis: key candidate targets were significantly enriched in multiple pathways related to heterotoxins. These key candidate targets were mainly derived two compounds: Hydroxysafflor Yellow A and Ferulic acid. Through the protein docking between S-protein and ACE2, it was found that Glu329 / Gln325 and Gln42 / Asp38 in ACE2 were played an important role in the binding process. The virtual calculation results of molecular docking show that Hydroxysafflor Yellow A and Ferulic acid can stably bind to Gln325 and Gln42 / Asp38 in ACE2, respectively, hindering the affinity of S-protein to ACE2. Conclusion Hydroxysafflor Yellow A and Ferulic acid can effectively interfere with the binding of the novel coronavirus S-protein to human ACE2 through a synergistic effect between molecules. Hydroxysafflor Yellow A and Ferulic acid can be used as potential inhibitors of SARS-CoV-2 for further research and development.