In Silico Target Analysis of Treatment for COVID-19 Using Huang-Lian-Shang-Qing-Wan, a Traditional Chinese Medicine Formula

Abstract

Due to the significantly negative impact of the coronavirus (CoV) disease (COVID-19) pandemic on the health of the community and the economy, it remains urgent and necessary to develop a safe and effective treatment method for COVID-19. Huang-Lian-Shang-Qing-Wan (HLSQW) is a herbal formula of traditional Chinese medicine (TCM) that has been applied extensively for treating “wind-heat-associated” symptoms in the upper parts of the body. The objective of the present in silico study was to investigate the potential effects of HLSQW in the context of severe acute respiratory syndrome (SARS)-CoV-2 infection. We analyzed the possible interactions between bioactive compounds within HLSQW on targets that may confer antiviral activity using network pharmacology and pharmacophore-based screening. HLSQW was found to potentially target a number of pathways and the expression of various genes to regulate cell physiology and, consequently, the anti-viral effects against SARS-CoV-2. Bioactive compounds contained within HLSQW may exert combined effects to reduce the production of proinflammatory factors, which may trigger the “cytokine storm” in patients with severe COVID-19. Results from molecular modeling suggested that the bioactive HLSQW components puerarin, baicalin, and daidzin exhibit high binding affinity to the active site of 3-chymotrypsin-like cysteine protease (3CLpro) to form stable ligand-protein complexes, thereby suppressing SARS-CoV-2 replication. In addition, our results also demonstrated protective effects of the HLSQW extract against cell injury induced by the proinflammatory cytokines tumor necrosis factor-α, interleukin (IL)-1β, and IL-6, against reactive oxygen species production and nuclear factor-κB activity in normal human lung cells in vitro. To conclude, HLSQW is a potential TCM remedy that warrants further study with the aim of developing an effective treatment for COVID-19 in the future.

Protective effects of Jing-Si-herbal-tea in inflammatory cytokines-induced cell injury on normal human lung fibroblast via multiomic platform analysis

“…At present, the most significant threat of COVID-19 to human beings is severe infection cytokine storm, resulting in multiorgan failure, which strains the capacities of emergency and hospital services. Further research on antiviral agents and vaccines to prevent the cytokine storm and anti-inflammatory response caused by SARS-CoV-2 remains a major focus in drug discovery and development[ 2 , 23 ]. Clinical evidence has demonstrated that Chinese herbal medicines and/or TCMs may be helpful in preventing or treating human coronavirus-related disorders[ 2 , 20 , 22 , 23 , 32 ].…”

“…Subsequently, PharmaDB’s database of 16,035 pharmacophore models served as the screening basis for every JSHT component. Furthermore, network analysis target outcomes were acquired using IPA software[ 22 , 23 ].…”

“…Chromatographic separation was conducted on an Atlantis T3 column (2.1 mm × 150 mm, 3 μm) maintained at 35°C using a binary mobile phase composed of 0.1% formic acid in water (solvent A) and 0.1% formic acid in acetonitrile (solvent B) at the flow rate of 0.25 mL/min following a gradient elution procedure: 0–2 min: 0%–2% solvent B; 2–21 min: 2%–99% solvent B; 21–26 min: 99% solvent B; 26–26.5 min: 99%–100% solvent B; 26.5–30 min: 2% solvent B. The volume injected was 5 μL[ 23 , 24 ].…”

“…The cells were maintained in a 75-T culture flask and cultured in DMEM supplemented with 2 mM L-glutamine, 10% FBS, 100 U/mL penicillin, and 100 μg/mL streptomycin. The culture was incubated at 37°C in a humidified atmosphere with 5% CO 2 [ 22 , 23 , 25 ]. HEL 299 cells were seeded in 24-well plates at a density of 2.5 × 10 5 cells per milliliter per well.…”

“…The molecular networks in the QIAGEN knowledge base originated from the focus molecules, with each molecule being interconnected with others in the network. This analysis was performed in duplicate[ 22 , 23 ].…”