Systematic identification of chemical components in Fufang Shuanghua oral liquid and screening of potential active components against SARS-CoV-2 protease.

Coronavirus disease (COVID-19) caused by SARS-COV-2 infection has been widely prevalent in many countries and has become a common challenge facing mankind. Traditional Chinese medicine (TCM) has played a prominent role in this pandemic, and especially TCM with the function of "heat-clearing and detoxifying" has shown an excellent role in anti-virus. Fufang Shuanghua oral liquid (FFSH) has been used to treat the corresponding symptoms of influenza such as fever, nasal congestion, runny nose, sore throat, and upper respiratory tract infections in clinic, which are typical symptoms of COVID-19. The content of chlorogenic acid, andrographolide and dehydrated andrographolide as the quality control components of FFSH is not less than 1.0 mg/mL, 60 µg/mL and 60 µg/mL respectively. In this study, UPLC-Q-TOF-MS/MS was employed to describe the chemical profile of FFSH. Virtual screening and fluorescence resonance energy transfer (FRET) were used to screen the effective components of FFSH acting on SARS-CoV-2 main protease (Mpro). As a result, 214 compounds in FFSH were identified or preliminarily characterized by UPLC-Q-TOF-MS/MS, and 61 active ingredients with potential inhibitory effects on Mpro were selected through receptor-based and ligand-based virtual screening. In particular, quercetin, forsythoside A, and linoleic acid showed a good inhibitory effect on Mpro in FRET evaluation with IC50 values of 26.15 µM, 22.26 µM and 47.09 µM respectively, and had a strong binding affinity with the receptor Mpro (6LU7) in molecular docking. CYS145 and HIS41 were the main amino acid residues affected by small molecules in the protein binding domain. In brief, we characterized, for the first time, 214 chemical components in FFSH, and three of them, including quercetin, forsythoside A and linoleic acid, were screened out to exert beneficial anti-COVID-19 effects through CYS145 and HIS41 sites, which may provide a new research strategy for TCM to develop new therapeutic drugs against COVID-19.

[Exploration on scientific connotation of TCM syndromes and recommended prescriptions against COVID-19 based on TCMTP V2.0].

Coronavirus disease 2019(COVID-19) has attracted great attentions from the whole world. Traditional Chinese medicine(TCM) has been widely used and shown satisfying efficacies in treating all stages of COVID-19. In this study, the molecular interaction networks of different stages of COVID-19(the early, severe, critical and recovery stage) were constructed using the links among symptoms-related genes collected from TCMIP V2.0(http://www.tcmip.cn/), an integrated pharmacology network-computing platform for TCM. Following the network topological feature calculation and functional enrichment analysis, we found that the molecular targets and pathways related with the "immune-inflammation system" were involved throughout all the stages of COVID-19. The severe stage and the critical period of COVID-19 were occupied by a large proportion of inflammatory factors and pathways, suggesting that there might be a cytokine storm in these periods, along with respiratory disorders, cardiopulmonary dysfunction, nervous system disorders, etc. Accordingly, the therapeutic targets and pathways hit by the recommended prescriptions against COVID-19 were also aimed to regulate the balance of immune-inflammation system, nutrient absorption and metabolism, abnormal energy metabolism, the cardio-pulmonary function, nerve system function, etc., which may be related to the therapeutic effects of these prescriptions in terms of several clinical symptoms, such as expiratory dyspnea, chest tightness and shortness of breath, abdominal distension and constipation, sweating and limb cold, dizziness, and irritability, etc. The above findings reflect the integrative actions of TCM characterizing by multiple-components, multiple-targets, multiple-pathways, and multiple-effects. This study systematically constructed the molecular networks of different TCM syndromes during the development and progression of COVID-19 and uncovered the biological basis for symptomatic treatment of TCM. Furthermore, our data revealed the pharmacological mechanisms and the scientific connotation of recommended prescriptions, which may provide supports for the prevention and treatment of COVID-19 using TCM.