From the end of December 2019 to the present, the novel coronavirus has ravaged the whole country. At present, there is still a lack of specific drugs for the treatment of COVID-19, and the existing chemical drugs can only alleviate some symptoms.Mongolian doctors have a comprehensive understanding of infectious diseases in long-term medical practice, and have accumulated rich experience in prevention and treatment. Mongolian doctors call acute infectious diseases plagues. According to The Four Medical Books - Secrets Book, there are sometimes five kinds of infectious disease: epidemics, acne, intestinal tingling,diphtheria,flu. Mongolian medicine summarizes various infectious diseases as "sticky" symptom caused by sticky insects that are invisible to the naked eye.Mongolian medicine also believes that factors such as abnormal weather, overwork, sadness, stench, anger, fear, diet or unclean food can reduce and disregulate the functioning of the body, giving opportunities for the invasion and activities of slime molds. The slime molds enters the body through the pore or a slight injury in skin, as well as the respiratory tract and esophagus, and then runs through the whole body with blood. Different plagues occur due to different areas of slime molds invasion and different predilecting sites[16].
The development and research cycle of new drugs based on clinical experiments are long and expensive, which is difficult to apply to clinical treatment in a timely manner. Moreover, the novel coronavirus has high infectiousness and variability,and the research requires high-protection level of laboratory conditions, which greatly restricts drug screening. So based on the fast speed of computer-aided drug design and could save the cost of drug development, it is suitable for large-scale screening of the chemical composition of traditional Chinese medicine. Molecular docking can simulate the force between the three-dimensional structure of the receptor and the ligand, then find a low-energy binding mode between the ligand and the receptor active site, which is fast, efficient and low-cost.
Ferulic acid is a kind of phenolic acid, which is widely found in natural plants. Ferulic acid is often cross-linked with lignin and polysaccharides to form part of the cell wall of a plant, rarely in a free state[17]. Ferulic acid is an effective monomer extracted from various traditional Chinese medicines such as Resina Ferulae, Chuanxiong Rhizoma, Equiseti Hiemalis Herba, Cimicifugae Rhizoma. It has a strong antioxidant ability and plays a great role in anti-tumor, anti-oxidant, detoxification, liver preservation,. Because of its stable nature and low toxicity, it has attracted widespread attention from people[18].Ferulic acid can significantly inhibit cold virus, HIV and Respiratory Syncytosis virus (RSV). Using influenza virus to infect the macrophages RAW264.7 of rats, the experiment found that if it treated by ferulic acid and isoarweiic acid, the production of interferon-8 was reduced, and the in-vivo experiment showed the same trend [19]. Hirabayashi [20] and others use the same cell line to observe and study the effects of ferulic acid on RSV-induced inflammatory protein-2. The results show that ferulic acid can significantly reduce the production of this protein. At the same time, ferulic acid and its derivatives have the effect of inhibiting HIV, which makes it considered one of the potential chemotherapy agents [21, 22].In addition, because Xanthine oxidase is associated with certain inflammatory diseases, the mechanism of ferulic acid inhibiting the virus may also be closely related to its inhibitory enzyme activity.
Carthami Flos is a traditional Chinese medicine for activating blood circulation and removing blood stasis.Safflower yellow pigment is a water-soluble active ingredient extracted from Carthami Flos. It is the main medicinal composition of Carthami Flos and belongs to flavonoids.Hydroxyl safflower yellow A(HSYA) is a clear and effective monomer component. The molecule formula is C27H32O16, which belongs to the small molecule charone glucoside substance[23].As the main potency substance, HSYA has a good effect of activating blood circulation and removing thrombus, reducing ischemia damage to the heart and brain, and it also has the functions of antioxidant, anti-inflammatory reactions and anti-angiogenesis of tumors[24].The antiviral effect of safflower yellow pigment A needs to be further studied.
In summary, This research adopts a research strategy that combines network pharmacology analysis, protein docking, and molecular docking virtual computing.We found that the hydroxysafflor yellow A and ferulic acid in Nagebu-9 can block the combination of SARS-CoV-2 S-protein and ACE2 at the molecular level, thereby inhibiting the spread of the virus between humans.Hydroxysafflor yellow A and ferulic acid can effectively prevent and control the new coronavirus through the synergistic effect of molecules. Both can be used as potential inhibitors of SARS-CoV-2 for further research and development.The relevant research results of this experiment will provide a theoretical basis for Nagebu-9's anti-new coronavirus, and also provide a methodological reference for the study of the mechanism of antiviral active ingredients of Chinese medicine.We aim to provide reference for the further development of the treatment plan of Sino-Mongolian medicine against the novel coronavirus epidemic, but due to the insufficient understanding of chemical components, the insufficient understanding of viruses and diseases, and the limitations of molecular docking itself, the results obtained may be biased. Post-term research should also be verified at multiple levels through pharmacodynamic evaluation, metabolomics and single target.