ABSTRACT
Since December 2019, severe acute respiratory syndrome coronavirus 2 has been found to be the culprit in the coronavirus disease 2019 (COVID-19), causing a global pandemic. Despite the existence of many vaccine programs, the number of confirmed cases and fatalities due to COVID-19 is still increasing. Furthermore, a number of variants have been reported. Because of the absence of approved anti-coronavirus drugs, the treatment and management of COVID-19 has become a global challenge. Under these circumstances, drug repurposing is an effective method to identify candidate drugs with a shorter cycle of clinical trials. Here, we summarize the current status of the application of drug repurposing in COVID-19, including drug repurposing based on virtual computer screening, network pharmacology, and bioactivity, which may be a beneficial COVID-19 treatment.
ABSTRACT
Traditional Chinese medicine (TCM) had demonstrated effectiveness in the prevention and control of COVID-19. Statistics showed that Ephedra and Glycyrrhiza were frequently used in the treatment of COVID-19. We hypothesized that the Ephedra-Glycyrrhiza drug pair is a potential choice for the treatment of COVID-19. Here, 112 active compounds were identified from Ephedra-Glycyrrhiza via network pharmacology approach. Ephedra-Glycyrrhiza pair enrichment analysis demonstrated that these compounds might participate in the cAMP, PI3K-Akt, JAK-STAT and chemokine signaling pathways, which had a high correlation with respiratory, nervous, blood circulation and digestive system-related diseases. Pathway analysis between Ephedra-Glycyrrhiza and COVID-19 showed that the key targets were TNF-α, IL2, FOS, ALB, and PTGS2. They might control PI3K-Akt signaling pathway to exert immune regulation, organ protection and antiviral effects. Molecular docking results showed that the active compounds from the Ephedra-Glycyrrhiza pair bound well to COVID-19 related targets, including the main protease (Mpro, also called 3CLpro), the spike protein (S protein), and the angiotensin-converting enzyme 2 (ACE2). The Molecular dynamics simulation was analyzed for the stability and flexibility of the complex. In conclusion, our study elucidated the potential pharmacological mechanism of Ephedra-Glycyrrhiza in the treatment of COVID-19 through multiple targets and pathways.
Subject(s)
Antiviral Agents/pharmacology , COVID-19 Drug Treatment , Drugs, Chinese Herbal/pharmacology , Ephedra/chemistry , Glycyrrhiza/chemistry , SARS-CoV-2/drug effects , Angiotensin-Converting Enzyme 2/metabolism , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , COVID-19/metabolism , Drug Combinations , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/therapeutic use , Humans , Molecular Docking Simulation , Protein Interaction Maps/drug effects , SARS-CoV-2/physiology , Signal Transduction/drug effects , Spike Glycoprotein, Coronavirus/metabolismABSTRACT
The Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 has been rapidly spreading globally and has caused worldwide social and economic disruption. Currently, no specific antiviral drugs or clinically effective vaccines are available to prevent and treat COVID-19. Traditional Chinese medicine (TCM) can facilitate syndrome differentiation and treatment according to the clinical manifestations of patients and has demonstrated effectiveness in epidemic prevention and control. In China, TCM intervention has helped to control the epidemic; however, TCM has not been fully recognized worldwide. In this review, we summarize the epidemiology and etiological characteristics of severe acute respiratory syndrome coronavirus 2 and the prevention and treatment measures of COVID-19. Additionally, we describe the application of TCM in the treatment of COVID-19 and the identification of small molecules of TCM that demonstrate anti-coronavirus activity. We also analyze the current problems associated with the recognition of TCM. We hope that, through the contribution of TCM, combined with modern technological research and the support of our international counterparts, COVID-19 can be effectively controlled and treated.