Research progress of antiviral material basis and mechanism of Compound Qinlan Oral Liquid.

Compound Qinlan Oral Liquid (,CQOL) is derived from Yinqiao San (), which is composed of Jinyinhua (Lonicerae Japonicae Flos), Huangqin (Scutellariae Radix), Lianqiao (Forsythiae Fructus) and Banlangen (Isatidis Radix). It is a common clinical herbal medicine for clearing heat and detoxification, and has antiviral effects. By reviewing the active ingredients of CQOL and the research progress on its anti-influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) efficacy, with view to providing a basis for the clinical use of CQOL in treatment of respiratory diseases caused by SARS-CoV-2.Copyright © 2023 Editorial Office of Chinese Traditional and Herbal Drugs. All rights reserved.

Current status and hotspot of Lonicera Japonica Flos research based on bibliometrics.

In order to comprehensively understand the research hotspots and development trends of Lonicera Japonica Flos in the past 20 years, and to provide intuitive data reference and objective opinions and suggestions for subsequent related research in this field, this study collected 8 871 Chinese literature and 311 English literature related to Lonicera Japonica Flos research in the core collection databases of Wanfang Data), CNKI and Web of Science (WOS) from 2002 to 2021, and conducted bibliometric and visual analysis using vosviewer. The results showed that the research on the active components of Lonicera Japonica Flos based on phenolic acid components, the research on the mechanism of novel coronavirus pneumonia based on data mining and molecular docking technology, and the pharmacological research on the anti-inflammatory and antiviral properties of Lonicera Japonica Flos are the three hot research directions in the may become the future research direction. In this paper, we analyze the research on Lonicera Japonica Flos from five aspects: active ingredients, research methods, formulation and preparation, pharmacological effects and clinical applications, aiming to reveal the research hotspots, frontiers and development trends in this field and provide predictions and references for future research.Copyright © Drug Evaluation Research 2022.

Research progress of antiviral material basis and mechanism of Compound Qinlan Oral Liquid.

Compound Qinlan Oral Liquid (,CQOL) is derived from Yinqiao San (), which is composed of Jinyinhua (Lonicerae Japonicae Flos), Huangqin (Scutellariae Radix), Lianqiao (Forsythiae Fructus) and Banlangen (Isatidis Radix). It is a common clinical herbal medicine for clearing heat and detoxification, and has antiviral effects. By reviewing the active ingredients of CQOL and the research progress on its anti-influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) efficacy, with view to providing a basis for the clinical use of CQOL in treatment of respiratory diseases caused by SARS-CoV-2.Copyright © 2023 Editorial Office of Chinese Traditional and Herbal Drugs. All rights reserved.

Jing Si Herbal Drink as a prospective adjunctive therapy for COVID-19 treatment: Molecular evidence and mechanisms

Background: SARS-CoV-2 has led to a sharp increase in the number of hospitalizations and deaths from pneumonia and multiorgan disease worldwide;therefore, SARS-CoV-2 has become a global health problem. Supportive therapies remain the mainstay treatments against COVID-19, such as oxygen inhalation, antiviral drugs, and antibiotics. Traditional Chinese medicine (TCM) has been shown clinically to relieve the symptoms of COVID-19 infection, and TCMs can affect the pathogenesis of SARS-CoV-2 infection in vitro. Jing Si Herbal Drink (JSHD), an eight herb formula jointly developed by Tzu Chi University and Tzu Chi Hospital, has shown potential as an adjuvant treatment for COVID-19 infection. A randomized controlled trial (RCT) of JSHD as an adjuvant treatment in patients with COVID-19 infection is underway Objectives: This article aims to explore the efficacy of the herbs in JSHD against COVID-19 infection from a mechanistic standpoint and provide a reference for the rational utilization of JSHD in the treatment of COVID-19. Method(s): We compiled evidence of the herbs in JSHD to treat COVID-19 in vivo and in vitro. Result(s): We described the efficacy and mechanism of action of the active ingredients in JSHD to treat COVID-19 based on experimental evidence. JSHD includes 5 antiviral herbs, 7 antioxidant herbs, and 7 anti-inflammatory herbs. In addition, 2 herbs inhibit the overactive immune system, 1 herb reduces cell apoptosis, and 1 herb possesses antithrombotic ability. Conclusion(s): Although experimental data have confirmed that the ingredients in JSHD are effective against COVID-19, more rigorously designed studies are required to confirm the efficacy and safety of JSHD as a COVID-19 treatment.Copyright © 2021

Antiviral and Anti-SARS-CoV-2 Activity of Natural Chlorogenic Acid and Its Synthetic Derivatives

Since the dawn of time, several viral epidemics have swept the globe, among them the current COVID-19 outbreak. The ongoing emergence and propagation of novel viral illnesses have compelled researchers to seek new therapeutic approaches that can get beyond the drawbacks of antivirals that are available right now. Medicinal plants have historically offered treatments for a range of illnesses. These bioactive compounds serve as the foundation for many "modern" pharmaceuticals. One of the essential polyphenols in various medicinal plants is Chlorogenic acid (CA), an ester of caffeic and quinic acid. Extensive research has revealed that CA possesses anti-inflammatory, anticarcinogenic, and antioxidant properties. This review aims to briefly summarise CA and its derivative's antiviral properties on various human viral diseases and their ability to fight the current COVID-19 disease. This review summarises CA antiviral action on the following viruses: influenza A virus (H1N1/H3N2/H7N9), hepatitis C virus (HCV) and hepatitis B virus (HBV), human immunodeficiency virus (HIV), infectious bronchitis virus (IBV), porcine reproductive and respiratory syndrome virus (PRRSV), herpes simplex virus (HSV)-1, enterovirus 71 (Ent 71), adenoviruses (AdenV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This review will open the way for developing and designing potentially effective and broad-spectrum CA-based antiviral medicines.

Interactive deciphering electron-shuttling characteristics of Coffea arabica leaves and potential bioenergy-steered anti-SARS-CoV-2 RdRp inhibitor via microbial fuel cells.

Due to the pandemics of COVID-19, herbal medicine has recently been explored for possible antiviral treatment and prevention via novel platform of microbial fuel cells. It was revealed that Coffea arabica leaves was very appropriate for anti-COVID-19 drug development. Antioxidant and anti-inflammatory tests exhibited the most promising activities for C. arabica ethanol extracts and drying approaches were implemented on the leaf samples prior to ethanol extraction. Ethanol extracts of C. arabica leaves were applied to bioenergy evaluation via DC-MFCs, clearly revealing that air-dried leaves (CA-A-EtOH) exhibited the highest bioenergy-stimulating capabilities (ca. 2.72 fold of power amplification to the blank). Furthermore, molecular docking analysis was implemented to decipher the potential of C. arabica leaves metabolites. Chlorogenic acid (-6.5 kcal/mol) owned the highest binding affinity with RdRp of SARS-CoV-2, showing a much lower average RMSF value than an apoprotein. This study suggested C. arabica leaves as an encouraging medicinal herb against SARS-CoV-2.

Identification of Potential Inhibitors for Severe Acute Respiratory Syndrome-related Coronavirus 2 (SARS-CoV-2) Angiotensin-converting Enzyme 2 and the Main Protease from Anatolian Traditional Plants

Background: The 2019 novel coronavirus disease (COVID-19) has caused a global health catastrophe by affecting the human population around the globe. Unfortunately, there is no specific medi-cation or treatment currently available for COVID-19. Objective: It is extremely important to find effective drug treatment in order to put an end to this pandemic period and return to normal daily life. In this context and considering the urgency, rather than focusing on the discovery of novel compounds, it is critical to explore the effects of existing herbal agents with proven antiviral properties on the virus. Methods: Molecular docking studies were carried out employing three different methods, Glide extra precision (XP) docking, induced fit docking (IFD), and molecular mechanics/generalized born surface area (MM/GBSA), to determine the potential antiviral and antibacterial effects of 58 phytochemicals present in Rosmarinus officinalis, Thymbra spicata, Satureja thymbra, and Stachys lavandulifolia plants against the main protease (Mpro) and angiotensin-converting enzyme 2 (ACE2) enzymes. Results: 7 compounds stood out among all the molecules, showing very high binding affinities. Accord-ing to our findings, the substances chlorogenic acid, rosmarinic acid, and rosmanol exhibited extremely significant binding affinities for both Mpro and ACE2 enzymes. Furthermore, carnosic acid and alpha-cadinol showed potent anti-Mpro activity, whereas caffeic acid and carvacrol exhibited promising anti-ACE2 activity. Conclusion: Chlorogenic acid, rosmarinic acid, rosmanol, carnosic acid, alpha-cadinol, caffeic acid, and carvacrol compounds have been shown to be powerful anti-SARS-CoV-2 agents in docking simulations against Mpro and ACE2 enzymes, as well as ADME investigations.

Explore mechanism of blood components Lonicerae Japonicae Flos intervening COVID-19 based on network pharmacology and molecular docking technology

Objective To explore the mechanism of Lonicerae Japonicae Flos (LJF) intervening COVID-19 by network pharmacology and molecular docking. Methods The potential targets of ingredients in serum of LJF were searched by Swiss Target Prediction and Similarity Ensemble Approach platform, and to predict and screen the therapeutic targets of COVID-19 through GeneCards and CTD databases. Ingredients in serum-target pathway network model was established by Cytoscape 3.7.1 software. GO biological process enrichment analysis of anti-COVID-19 target genes in Lonicerae Japonicae Flos was performed by DAVID, and KEGG pathway enrichment analysis of anti-COVID-19 target genes in in serum of Lonicerae Japonicae Flos was performed by KOBAS 3.0. Results Ten ingredients in serum of Lonicerae Japonicae Flos such as hyperoside, 7-methoxycoumarin, 3-O-feruloylquinic acid, chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, dimethyl terephthalate, dibutyl sebacate, hexadecenoic acid, herboxidiene involved in PIK3R1, NFKB1, HRAS, IL6, TNF, TP53, CASP3, GRB2, GSK3B, JUN, MAPK10, MAPK14, MAPK8, PRKCA, and affected 27 mainly pathways involved in immune, inflammation, virus, nervous system, and so on. The molecular docking showed that the binding energy of hyperoside with the SARS-CoV-2 3CL hydrolase and ACE2 were most stable. Conclusion Ingredients in serum of Lonicerae Japonicae Flos may interfere proteins and pathways related to anti-inflammatory, antiviral immunity, antipyretic, analgesic and sedation to play a role against COVID-19. © Endocrinology Research Centre, 2022.

Inhibition of the SARS-CoV-2 3CLpro main protease by plant polyphenols.

The abundance of polyphenols in edible plants makes them an important component of human nutrition. Considering the ongoing COVID-19 pandemic, a number of studies have investigated polyphenols as bioactive constituents. We applied in-silico molecular docking as well as molecular dynamics supported by in-vitro assays to determine the inhibitory potential of various plant polyphenols against an important SARS-CoV-2 therapeutic target, the protease 3CLpro. Of the polyphenols in initial in-vitro screening, quercetin, ellagic acid, curcumin, epigallocatechin gallate and resveratrol showed IC50 values of 11.8 µM to 23.4 µM. In-silico molecular dynamics simulations indicated stable interactions with the 3CLpro active site over 100 ns production runs. Moreover, surface plasmon resonance spectroscopy was used to measure the binding of polyphenols to 3CLpro in real time. Therefore, we provide evidence for inhibition of SARS-CoV-2 3CLpro by natural plant polyphenols, and suggest further research into the development of these novel 3CLpro inhibitors or biochemical probes.

Computational and network pharmacology studies of Phyllanthus emblica to tackle SARS-CoV-2.

Background: Since December 2019, SARS-CoV-2 had been a significant threat globally, which has accounted for about two million deaths. Several types of research are undergoing and have reported the significant role of repurposing existing drugs and natural lead in the treatment of COVID-19. The plant Phyllanthus emblica (Synonym-Emblica officinalis) (Euphorbiaceae) is a rich source of vitamin C, and its use as an antiviral agent has been well established. Purpose: The present study was undertaken to investigate the potency of the several components of Phyllanthus emblica against three protein targets of 2019-nCoV viz. NSP15 endoribonuclease, main protease, and receptor binding domain of prefusion spike protein using molecular docking and dynamics studies. Methods: The docking simulation studies were carried out using Schrödinger maestro 2018-1 MM share version, while dynamics studies were conducted to understand the binding mechanism and the complexes' stability studies. Results: Out of sixty-six tested compounds, Chlorogenic acid, Quercitrin, and Myricetin were most effective in showing the highest binding energy against selected protein targets of SARS-CoV-2. The network pharmacology analysis study confirmed these compounds' role in modulating the immune response, inflammatory cascade, and cytokine storm through different signaling pathways. Conclusion: Current pharmacoinformatic approach shows possible role of Phyllanthus emblica in the treatment and management of COVID-19.

Caffeoylquinic acids: chemistry, biosynthesis, occurrence, analytical challenges, and bioactivity.

Caffeoylquinic acids (CQAs) are specialized plant metabolites we encounter in our daily life. Humans consume CQAs in mg-to-gram quantities through dietary consumption of plant products. CQAs are considered beneficial for human health, mainly due to their anti-inflammatory and antioxidant properties. Recently, new biosynthetic pathways via a peroxidase-type p-coumaric acid 3-hydroxylase enzyme were discovered. More recently, a new GDSL lipase-like enzyme able to transform monoCQAs into diCQA was identified in Ipomoea batatas. CQAs were recently linked to memory improvement; they seem to be strong indirect antioxidants via Nrf2 activation. However, there is a prevalent confusion in the designation and nomenclature of different CQA isomers. Such inconsistencies are critical and complicate bioactivity assessment since different isomers differ in bioactivity and potency. A detailed explanation regarding the origin of such confusion is provided, and a recommendation to unify nomenclature is suggested. Furthermore, for studies on CQA bioactivity, plant-based laboratory animal diets contain CQAs, which makes it difficult to include proper control groups for comparison. Therefore, a synthetic diet free of CQAs is advised to avoid interferences since some CQAs may produce bioactivity even at nanomolar levels. Biotransformation of CQAs by gut microbiota, the discovery of new enzymatic biosynthetic and metabolic pathways, dietary assessment, and assessment of biological properties with potential for drug development are areas of active, ongoing research. This review is focused on the chemistry, biosynthesis, occurrence, analytical challenges, and bioactivity recently reported for mono-, di-, tri-, and tetraCQAs.

Chlorogenic acid is a positive regulator of MDA5, TLR7 and NF-κB signaling pathways mediated antiviral responses against Gammacoronavirus infection.

Chlorogenic acid (CGA) is a phenolic compound that has been well studied for its antiviral, anti-inflammatory and immune stimulating properties. This research was aimed to focus on the antiviral properties of CGA on infectious bronchitis virus (IBV) in vivo and in vitro for the very first time. The outcome of in vitro experiments validated that, out of five previously reported antiviral components, CGA significantly reduced the relative mRNA expression of IBV-N in CEK cells. At high concentration (400 mg/kg), CGA supplementation reduced IBV-N mRNA expression levels and ameliorated the injury in trachea and lungs. The mRNA expression levels of IL-6, IL-1ß, IL-12, and NF-κB were considerably turned down, but IL-22 and IL-10 were enhanced in trachea. However, CGA-H treatment had considerably increased the expression levels of MDA5, MAVS, TLR7, MyD88, IRF7, IFN-ß and IFN-α both in trachea and lungs. Moreover, CGA-H notably induced the CD3+, CD3+ CD4+ and CD4+/CD8+ proliferation and significantly increased the IgA, IgG, and IgM levels in the serum. In conclusion, these results showed that at high concentration CGA is a strong anti-IBV compound that can effectively regulate the innate immunity through MDA5, TLR7 and NF-κB signaling pathways and have the potential to induce the cell mediated and humoral immune response in IBV infected chickens.

Chlorogenic acid, a natural product as potential inhibitor of COVID-19: virtual screening experiment based on network pharmacology and molecular docking.

Chlorogenic acid (CGA) is a potential inhibitor of Coronavirus Disease 2019 (COVID-19). ACE2 and its co-expressed proteins are SARS-CoV-2 receptors, which have been linked to SARS-CoV-2 infection and considered as the key target of SARS-CoV-2 in entering target cells. Here, network pharmacology was used to investigate the mechanism by which CGA affected COVID-19. A total of 70 potential targets related to the treatment of COVID-19 were obtained, among which NFE2L2, PPARG, ESR1, ACE, IL6, and HMOX1 might be the main potential targets. Finally, CGA and potential target proteins were scored by molecular docking, and the prediction results of network pharmacology were preliminarily verified. Moreover, CGA had potential anti-SARS-CoV-2 activity via integrating three common receptors in clinical practice compared with clinical trial drugs registered for the treatment of COVID-19, as shown by molecular docking. The mechanism of CGA against COVID-19 was initially investigated using network pharmacology, followed by molecular docking.

Effects of Lonicera japonica Flower Bud Extract on Citrobacter rodentium-Induced Digestive Tract Infection.

Background: Although antibiotic therapy is currently a gold standard for bacterial infections, it is not used for severe diseases like enterohemorrhagic Escherichia coli, in which the Shiga toxin is overproduced by antibiotic action. The Lonicera japonica flower bud (LJF) is an herbal component used against purulent diseases in traditional Japanese and Chinese medicine. We investigated the effects of LJF extract (LJFE) on Citrobacter rodentium-induced digestive tract infection in a mouse model. Methods:Citrobacter rodentium and LJFE were orally administered to C57BL/6 mice. The survival rate and bacterial colonization in the large intestine, mesenteric lymph node, and blood of mice were evaluated. Cytokines secreted from intraperitoneal macrophages of LJFE-treated mice were measured using ELISA. Moreover, the phagocytic activity of intraperitoneal macrophages against Citrobacter rodentium was compared between LJFE- or chlorogenic acid (CGA)-treated mice. Results: LJFE significantly increased the survival rate and decreased Citrobacter rodentium colonization in mice. Moreover, the values of tumor necrosis factor-α, interleukin-1ß, and interferon-γ secreted from macrophages were increased following LJFE treatment. While macrophages of LJFE-treated mice showed a significant phagocytic activity, macrophages of CGA-treated mice only showed a phagocytic tendency. Conclusions: LJF may be useful for treating Citrobacter rodentium-induced digestive tract infection.