ABSTRACT
In the face of the COVID-19 pandemic, there is still a lack of miracle drugs for treatment. Repurposing drugs such as Remdesivir and corticosteroids to treat COVID-19 are being studied. Traditional Chinese medicine was widely used during the outbreak of Severe Acute Respiratory Syndrome (SARS) coronavirus infection in China in 2003. It was found that standard medical treatment combined with Chinese medicine treatment may improve the symptoms of SARS patients and speeding resolution of lung infiltration. The commonly used prescriptions for preventing the coronavirus infection are Sangjuyin plus Yupingfeng powder. Various Traditional Chinese medicines with potential to fight SARS-CoV-2 include Liquorice Root and Rhizome, Rhubarb, Heartleaf Houttuynia Herb, Indi-gowoad Root, Tangerine Peel, Scutellaria Root, and Red Sage Root and Rhizome etc. In addition, Chinese patent medicines including Shuanghuanglian Oral liquid, Lianhua Qingwen Capsule, Jinhua Qinggan Granule and Taiwan Chingguan Yihau are recognized as plausible agents for the treatment of novel coronavirus pneumonia. The antiviral, anti-inflammatory and immunomodulatory effects of selected Chinese herbal drugs may attribute to their inhibiting the binding of the coronavirus spike protein to the angiotensin-converting enzyme 2 (ACE2) receptor, inhibiting key enzymes such as 3-chymotrypsin-like protease and ribonucleic acid (RNA)- dependent RNA polymerase during viral replication, and reducing pro-inflammatory cytokines. Since most of the relevant studies mentioned the potential anti-SARS-CoV-2 activity of these agents were only in vitro and animal experiments, more randomized double-blind controlled trials are needed to provide reliable evidence of clinical efficacy in future.
ABSTRACT
Objective: Yupingfeng Powder (YPF), a kind of preventative patent medicine, is chosen for treatment of coronavirus disease 2019 (COVID-19) due to its high frequency application in respiratory tract diseases, such as chronic obstructive pulmonary disease, asthma, respiratory tract infections, and pneumonia, with the advantage of reducing the relapse rate and the severity. However, the active components of YPF and the mechanisms of components affecting COVID-19 are unclear. This study aimed to determine active constituents and elucidate its potential mechanisms. Methods: Ultra performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q/TOF-MS) and liquid chromatography-triple quadrupole mass spectrometry (LC-QQQ-MS) were used to determine the components and absorbable constituents of YPF. Secondly, TCMSP, Drugbank, Swiss and PharmMapper were used to search the targets of absorbable bioactive constituents of YPF, and the targets of COVID-19 were identified based on GeneCards and OMIM databases. STRING database was used to filter the possible inter-protein interactions. Thirdly, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis were performed to identify molecular function and systemic involvement of target genes. Results: A total of 61 components of YPF and 36 absorbable constituents were identified through UPLC-Q/TOF-MS. Wogonin, prim-O-glucosylcimifugin, 5-O-methylvisamminol, astragaloside IV and 5-O-methylvisamminol (hydroxylation) were vital constituents for the treatment of COVID-19, and RELA, TNF, IL-6, MAPK14 and MAPK8ere recognized as key targets of YPF. The major metabolic reactions of the absorbed constituents of YPF were demethylation, hydroxylation, sulfation and glucuronidation. GO and KEGG pathway analysis further showed that the most important functions of YPF were T cell activation, response to molecule of bacterial origin, cytokine receptor binding, receptor ligand activity, cytokine activity, IL-17 signaling pathway, Chagas disease, lipid and atherosclerosis, etc. Conclusion: The approach of combining UPLC-Q/TOF-MS with network pharmacology is an effective tool to identify potentially bioactive constituents of YPF and its key targets on treatment of COVID-19.