ABSTRACT
COVID-19 pandemic has been a global outbreak of coronavirus (SARS-CoV-2 virus) since 2019. Taiwan Chingguan Yihau (NRICM101) is the first traditional Chinese medicine (TCM) classic herbal formula and is widely used for COVID-19 patients in Taiwan and more than 50 nations. This study is to investigate in silico target fishing for the components of NRICM101 and to explore whether NRICM101 inhibits cytokines-induced normal human lung cell injury in vitro. Our results showed that network prediction of NRICM101 by a high throughput target screening platform showed that NRICM101 has multiple functions that may affect cytokine regulation to prevent human lung cell injury. In addition, NRICM101 revealed protective effects against TNF-α/IL-1ß-induced normal human lung HEL 299 cell injury through JNK and p38MAPK kinase signaling. Next-generation sequencing (NGS) analysis of NRICM101 on TNF-α/IL-1ß-injured HEL 299 cells indicated that inflammatory pathway, cell movement of macrophages, cellular infiltration by macrophages, and Th1/Th2 immuno-regulation pathways were included. Thus, NRICM101 is a therapeutic agent, and it can improve COVID-19 syndrome to confer beneficial effects through multiple targeting and multiple mechanisms.
ABSTRACT
Coronavirus disease 2019 (COVID-19) has been spreading worldwide with a mind-boggling speed. According to a statement from World Health Organization (WHO), COVID-19 has infected more than six billions people and caused more than one and half million passing in the world. Based on previous experience with SARS, the Taiwanese government had decided to block viral transmission during its early stages. This review sums up the clinical characteristics, Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) viral infection process, diagnostic methods, preventive strategy, and the executive proportions of COVID-19, as well as the name-based mask distribution system (NBMDS) in Taiwan. We also give a review of the conceivable sub-atomic pharmacologic systems against SARS-CoV-2 specialists and the blend of remdesivir (GS-5734), chloroquine (CQ), and hydroxychloroquine (HCQ). Lastly, we summarized the therapeutic agents against COVID-19 as mentioned by COVID-19 treatment guidelines. In this review, development of novel anti-SARS-CoV-2 viral agents, vaccines for COVID-19 therapy or an effective combination therapy can be expected based on all the information accumulated. Last but not least, we might want to stretch out our best respects to all medical providers in their worldwide battle against COVID-19.
ABSTRACT
Negative impacts of COVID-19 on human health and economic and social activities urge scientists to develop effective treatments. Baicalin is a natural flavonoid, extracted from a traditional medicinal plant, previously reported with anti-inflammatory activity. In this study, we used pharmacophore fitting and molecular docking to screen and determine docking patterns and the binding affinity of baicalin on 3 major targets of SARS-CoV-2 (3-chymotrypsin-like cysteine protease [3CLpro], papain-like protease [PLpro], and RNA-dependent RNA polymerase). The obtained data revealed that baicalin has high pharmacophore fitting on 3CLpro and predicted good binding affinity on PLpro. Moreover, using the enzymatic assay, we examined the inhibitory effect of baicalin in vitro on the screened enzymes. Baicalin also exhibits inhibitory effect on these proteases in vitro. Additionally, we performed pharmacophore-based screening of baicalin on human targets and conducted pathway analysis to explore the potential cytoprotective effects of baicalin in the host cell that may be beneficial for COVID-19 treatment. The result suggested that baicalin has multiple targets in human cell that may induce multiple pharmacological effects. The result of pathway analysis implied that these targets may be associated with baicalin-induced bioactivities that are involved with signals of pro-inflammation factors, such as cytokine and chemokine. Taken together with supportive data from the literature, the bioactivities of bailalin may be beneficial for COVID-19 treatment by reducing cytokine-induced acute inflammation. In conclusion, baicalin is potentially a good candidate for developing new therapeutic to treat COVID-19.
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)-1?, and IL-6, against reactive oxygen species production and nuclear factor-?B 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.
ABSTRACT
The coronavirus disease 2019 (COVID19) outbreak, which has caused >46 millions confirmed infections and >1.2 million coronavirus related deaths, is one of the most devastating worldwide crises in recent years. Infection with COVID19 results in a fever, dry cough, general fatigue, respiratory symptoms, diarrhoea and a sore throat, similar to those of acute respiratory distress syndrome. The causative agent of COVID19, SARSCoV2, is a novel coronavirus strain. To date, remdesivir has been granted emergency use authorization for use in the management of infection. Additionally, several efficient diagnostic tools are being actively developed, and novel drugs and vaccines are being evaluated for their efficacy as therapeutic agents against COVID19, or in the prevention of infection. The present review highlights the prevalent clinical manifestations of COVID19, characterizes the SARSCoV2 viral genome sequence and life cycle, highlights the optimal methods for preventing viral transmission, and discusses possible molecular pharmacological mechanisms and approaches in the development of antiSARSCoV2 therapeutic agents. In addition, the use of traditional Chinese medicines for management of COVID19 is discussed. It is expected that novel antiviral agents, vaccines or an effective combination therapy for treatment/management of SARSCoV2 infection and spread therapy will be developed and implemented in 2021, and we would like to extend our best regards to the frontline health workers across the world in their fight against COVID19.