To Analyze the Mechanism of Glycyrrhiza uralensis (Licorice) in the Treatment of COVID-19 Based on Network Pharmacology and Molecular Docking Technology

Research Article

Ann Agric Crop Sci. 2023; 8(3): 1138.

To Analyze the Mechanism of Glycyrrhiza uralensis (Licorice) in the Treatment of COVID-19 Based on Network Pharmacology and Molecular Docking Technology

Junyi Zhang1; Xuhai Yang 1,2,3#; Lichun Zhu1; Ruiying He1; Shuangquan Xie1,4,*

1Shihezi University, China

2Xinjiang Production and Construction Corps Key Laboratory of Modern Agricultural Machinery, Shihezi University, China

3Engineering Research Center for Production Mechanization of Oasis Special Economic Crop, Ministry of Education, Shihezi University, China

4Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, Shihezi University, China

*Corresponding author: Shuangquan Xie Shihezi University, Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, Shihezi University, Shihezi 832002, China. Tel: 183-9983-7286 Email: xiesq0921@163.com

#These authors contributed equally to this work

Received: June 27, 2023 Accepted: July 27, 2023 Published: August 03, 2023

Abstract

The current study, the effectiveness of analyzing Glycyrrhiza uralensis for the treatment of COVID-19 was investigated using an integrated network pharmacology and molecular docking approach. Through network pharmacology, establishment of Protein-Protein Interactions (PPI), molecular docking simulations, GO analysis, and KEGG analysis, the aim was to investigate the mechanism of licorice in the treatment of COVID-19. There are 7 core genes corresponding to 3 bioactive compounds of G. uralensis. The target proteins of G. uralensis for the treatment of neocoronary pneumonia could be enriched to cancer pathway, lipid The target proteins of G. uralensis for the treatment of neocoronary pneumonia could be enriched to cancer pathway, lipid and atherosclerosis pathway, PI3K-Akt signaling pathway, and down-regulate the activity of core targets to inhibit the expression of virus SARS-CoV-2. Based on molecular docking simulations, the largest significant binding affinities were found for TNF and 7-Methoxy-2-methyl isoflavone (-6.95 kcal/mol), MAPK1 and kaempferol (-6.75 kcal/mol), and AKT1 and quercetin (-6.74 kcal/mol). Quercetin induces viral cell cycle arrest and inhibits growth and metastasis by engaging in the induction and expression of key intracellular targets. The flavonoid chemicals of kaempferol can inhibit inflammation-related signaling pathways and suppress the release of inflammation-related factors, and 7-methoxy-2-methylisoflavone may have therapeutic effects on COVID-19 by reducing hydroxyproline levels to suppress lung inflammation and fibrosis indices and modulate immune function. This suggests that G. uralensis has an interfering effect on novel coronaviruses and its main active component has a strong binding ability to the core gene of SARS-CoV-2, providing knowledge for future studies based on COVID-19.

Keywords: Glycyrrhiza uralensis; Novel coronavirus pneumonia; Network pharmacology; Molecular docking; Quercetin; Kaempferol

Introduction

Coronavirus Disease 2019 (COVID-19) is a Severe Acute Respiratory Syndrome Coronavirus that spreads through contact, aerosols, and direct contact. Acute respiratory infection brought on by the human body catching the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) [1,2]. Since the outbreak of New Crown, 651918402 people worldwide have now been infected, with a morbidity and mortality rate of approximately 2%. To date, the mechanism of treatment for New Crown pneumonia is unknown, and according to the available clinical cases [3,5]. In the context of universal vaccination, the rate of severe illness and mortality of the Omicron variant has fallen to levels similar to those of seasonal influenza (a more optimistic estimate is 0.3%, 0.1%). However, its ability to spread is much greater than that of seasonal influenza, and the base of the infected population will be much larger than that of seasonal influenza. Therefore, the level of threat to the health of the entire population and the pressure on the health system from the new coronavirus is much greater than that of seasonal influenza.

To date, the pharmaceutical community has made significant progress in mitigating the SARS-CoV-2 threat through the development of small-molecule drugs [6,7]. Gilead’s Veklury was conditionally approved to combat the outbreak [8] and Merck’s Lagevrio [9] raise hope for a COVID-19 cure. However, promising bullets still do not exist. As an indispensable resource for promising compounds, traditional medicine [10] and natural products [11,12] have attracted significant attention in countering SARS-CoV-2 infection.

Traditional Chinese medicine has been fighting against disease for thousands of years [13]. The benefit of Traditional Chinese Medicine (TCM) that "Prevention precedes disease" has been adequately mirrored in the prevention and treatment of epidemics, and TCM has had successful outcomes treating COVID-19 in various parts of China [14]. The main therapeutic mechanisms of herbal medicine for neoconjunctivitis include direct antiviral, anti-inflammatory effects, protection of target organs and immunomodulation [15], especially in terms of the cure rate of clinical symptoms such as TCM symptoms and pulmonary lesions, as well as prognosis [16]; however, there are no specific therapeutic drugs for neoconjunctivitis. Clinical evidence suggests that herbal medicines are effective against viral infections such as influenza, SARS and SARS-CoV-2 by targeting viral cell entry, viral replication and host authorities for the treatment of COVID-19. According to the frequency of herbal medicine use since the epidemic [17,18], Glycyrrhiza uralensis, almond, and raw gypsum were the top 3 drugs with the highest frequency of occurrence in the treatment of COVID-19. Recent reports also suggest that Glycyrrhiza uralensis extracts may play a potential role in the fight against COVID-19 and related diseases [19]. According to the Chinese Pharmacopoeia, Glycyrrhiza uralensis is able to strengthen the spleen, clear heat, detoxify and resolve phlegm, as well as stop cough, spasm and pain, thus harmonizing the effects of other drugs [20]. However, the specific mechanism of action of licorice with COVID-19 is still unclear, so this paper uses network pharmacology and molecular docking methods to analyze it.

Network pharmacology is a contemporary science that leverages data networks to explore biological mechanisms and pharmacological molecules, in accordance with the theoretical framework of systems biology [21-23]. A detailed inspection of the therapeutic mechanisms of molecules, cells, tissues, and other drugs in complex diseases is also made possible by it, in addition to new ideas and procedures for interdisciplinary research involving Chinese and Western medicine, artificial intelligence, and large-scale biomedical data analysis [24].

In the present investigation, we utilized a bioinformatics approach to screen the potentially useful small molecules of Glycyrrhiza uralensis. Neo-orange and Glycyrrhiza uralensis' primary cross-targets were examined. In order to investigate the mechanisms of action and potential pathways, Protein-Protein Interactions (PPI), KEGG, and Gene Ontology (GO) were employed to assess any potential linkages between the primary crossover targets. For the purpose of to investigate the mechanism of action of Glycyrrhiza uralensis for the treatment of new coronavirus pneumonia, seven major genes were screened to acquire their corresponding proteins to which the active molecules of Glycyrrhiza uralensis were docked.

Therefore, this study investigated the targets and molecular processes of Glycyrrhiza uralensis for the treatment of novel coronavirus pneumonia, and predicted the anti-novel coronavirus pneumonia effect of Glycyrrhiza uralensis using network pharmacology and molecular docking techniques, which could provide new ideas and necessary theoretical basis for clinical treatment. And the workflow of this study is presented in Figure 1.