Molecular docking prediction of three active components of Solidago esculenta against novel coronavirus
In December 2019, novel coronavirus SARS CoV-2 broke out rapidly in Wuhan, Hubei Province. As of June 22, 2020, there are 85018 confirmed cases of novel coronavirus disease 2019 (COVID-19) in China, including 4646 deaths. Subsequently, over 8.97 million cases of infection were reported in more than 200 countries worldwide, including the United States, Italy, Spain, the United Kingdom, France, Germany, Iran, Switzerland, South Korea, and Japan. The common symptoms of patients infected with SARS-CoV-2 are fever, cough, and muscle pain or fatigue. The S protein of SARS-CoV-2 is structurally similar to that of SARS-CoV, and both have significant binding affinity for angiotensin converting enzyme 2 (ACE2) on the surface of human cells, which enters the human body through ACE2 mediation. ACE2 is widely expressed in tissues and cells such as the lungs, digestive tract, and kidneys, and is currently believed to be the key for SARS-CoV-2 to enter host cells. Clinical treatment has shown that traditional Chinese medicine combined with Western medicine has significant therapeutic effects on COVID-19. So far, there is still a lack of specific drugs for the treatment of COVID-19. Therefore, there is an urgent need to find effective antiviral drugs to curb this disease.
The Paris polyphylla plant in the Liliaceae family, also known as the flea rest, grass river cart, and white sweet lily, has a root and stem called the Paris polyphylla. Chonglou, as a traditional Chinese medicine with a long history of medicinal use, has anti-inflammatory, hemostatic, bactericidal, sedative, analgesic, anti asthmatic, and cough relieving effects. It is also used in folk medicine to treat various types of sores, carbuncles, venomous snake bites, etc. Since the 1970s, research on active ingredients in heavy buildings has continued. At present, over a hundred chemical components have been discovered in the heavy buildings, among which more than 70 are steroidal saponins. And the steroidal saponins with higher content in Chonglou include dioscin and saponins of spirostanol. Polyphyllin I, Polyphyllin VI, and Polyphyllin VII all belong to the category of dioscin (Figure 1), which is abundant in Polygonatum sibiricum and widely used in the treatment of various diseases, including anti-tumor, immune regulation, antibacterial effects, etc. Zhonglou saponins are spiral steroid saponins; Saponins are composed of aglycones and sugars, glucuronic acids, or other organic acids. It contains a common parent nucleus in its structure (Figure 1), which consists of six rings and 27 carbon atoms, with A, B, C, and D being steroid parent nuclei (cyclopentane dihydrophenanthrene). The steroid nucleus is connected to a furan ring E and a pyran ring F. And it is often connected in the form of spiroketide. In this paper, molecular docking method was used to explore the active compounds of Chinese herbal medicine Yizhihua Aesculus for the treatment of novel coronavirus SARS-CoV-2. SARS-CoV-2 mainly binds to the angiotensin-converting enzyme 2 (ACE2) receptor on the surface of human cells through its S protein. This study predicted the binding affinity of three types of saponins (I, VI, VII) rich in Polygonatum sibiricum with ACE2 through molecular docking simulation

Due to SARS-CoV-2 being a newly discovered virus, there is currently no confirmed or available specific drug. The economically effective treatment strategy is to utilize existing drugs. Clinical treatment has shown that the combination of traditional Chinese medicine and Western medicine has significant therapeutic effects on COVID-19. Therefore, screening existing drugs extracted from traditional Chinese medicine is an effective strategy. Previous studies have found that chloroquine is highly effective in controlling SARS-CoV-2 infection in vitro. Chloroquine is a 4-aminoquinoline that, in addition to being primarily used as an antimalarial drug, can also inhibit viral replication by reducing the terminal glycosylation of ACE2 receptors and interfering with the binding of SARS-CoV-2 to ACE2 receptors. Cheng et al. used molecular docking to calculate the binding energy between chloroquine and ACE2. The results showed that chloroquine has potential binding ability with ACE2, with a binding free energy of -5.70 kcal/mol and binding sites of Leu-95, Gln-58, and Gln-102. Compared with chloroquine, the docking binding free energies of the three saponins with ACE2 are lower. Recently, with the global spread of SARS-CoV-2 infection, more and more researchers have been involved in the screening of anti SARS-CoV-2 drugs. Yan et al. screened 38 Chinese patented drugs for ACE (PDB: 1R4L) and the main M protease of the virus (PDB: 6LU7) through molecular docking, and discovered 10 potential anti SARS-CoV-2 drugs including artemisinin, rutin, glycyrrhizin, puerarin, andrographolide, and matrine. Liu et al. found through network pharmacology and molecular docking studies that luteolin (-26.78 kJ/mol), quercetin (-26.36 kJ/mol), and demethylated icariin (-25.94 kJ/mol) bind to SARS-CoV-2 3CL hydrolase. Some drugs may have lower docking activity with ACE2, but this does not mean they are not suitable for COVID-19 treatment, as docking simulations only provide a reference for preliminary research. In addition, the principles for formulating traditional Chinese medicine prescriptions include eliminating pathogenic invasion and enhancing the body’s resistance. Therefore, we cannot rule out the possibility that some drugs may have an effect on COVID-19 by regulating the immune system. Further experiments are necessary to verify whether these steroidal saponins can target ACE2 and prevent SARS-CoV-2 infection in cell culture models and experimental animals.