Search

Salvianolic acid B (SalB), among the most abundant bioactive polyphenolic compounds found in Salvia miltiorrhiza Bge., exerts therapeutic and protective effects against various diseases. Although some summaries of the activities of SalB exist, there is lack of a scientometric and in-depth review regarding disease therapy. In this review, scientometrics was employed to analyze the number of articles, publication trends, countries, institutions, keywords, and highly cited papers pertaining to SalB research. The scientometric findings showed that SalB exerts excellent protective effects on the heart, lungs, liver, bones, and brain, along with significant therapeutic effects against atherosclerosis (AS), Alzheimer's disease (AD), liver fibrosis, diabetes, heart/brain ischemia, and osteoporosis, by regulating signaling pathways and acting on specific molecular targets. Moreover, this review delves into in-depth insights and perspectives, such as the utilization of SalB in combination with other drugs, the validation of molecular mechanisms and targets, and the research and development of novel drug carriers and dosage forms. In conclusion, this review aimed to offer a comprehensive scientometric analysis and in-depth appraisal of SalB research, encompassing both present achievements and future prospects, thereby providing a valuable resource for the clinical application and therapeutic exploitation of SalB. [ABSTRACT FROM AUTHOR]

Introduction: In recent years, graph neural network has been extensively applied to drug discovery research. Although researchers have made significant progress in this field, there is less research on bibliometrics. The purpose of this study is to conduct a comprehensive bibliometric analysis of graph neural network applications in drug discovery in order to identify current research hotspots and trends, as well as serve as a reference for future research. Methods: Publications from 2017 to 2023 about the application of graph neural network in drug discovery were collected from the Web of Science Core Collection. Bibliometrix, VOSviewer, and Citespace were mainly used for bibliometric studies. Results and Discussion: In this paper, a total of 652 papers from 48 countries/regions were included. Research interest in this field is continuously increasing. China and the United States have a significant advantage in terms of funding, the number of publications, and collaborations with other institutions and countries. Although some cooperation networks have been formed in this field, extensive worldwide cooperation still needs to be strengthened. The results of the keyword analysis clarified that graph neural network has primarily been applied to drugtarget interaction, drug repurposing, and drug-drug interaction, while graph convolutional neural network and its related optimization methods are currently the core algorithms in this field. Data availability and ethical supervision, balancing computing resources, and developing novel graph neural network models with better interpretability are the key technical issues currently faced. This paper analyzes the current state, hot spots, and trends of graph neural network applications in drug discovery through bibliometric approaches, as well as the current issues and challenges in this field. These findings provide researchers with valuable insights on the current status and future directions of this field. [ABSTRACT FROM AUTHOR]

The pharmaceutical sector has recently witnessed a transformative improvement and shift toward artificial intelligence (AI) in its drug and pharmaceutical delivery process and procedures. Hence, this research delves into the benefits and obstacles pharmaceutical firms face in utilizing AI in China. Globally, China is recognized as a dominant pillar in research and development in the pharmaceutical industry. The country has incorporated AI approaches and technologies to improve the drug industry's cost, efficiency and development. Therefore, this study applies the case study method and evaluation of prior studies to assess AI's potential benefits and challenges in the drug and pharmaceutical enterprises. The research provided an in-depth evaluation of AI in the various phases of the drug discovery process. The research outcome indicated that AI's benefits include drug repurposing, target identification, clinical trial optimization, quality assurance, and control and efficient drug distribution method. However, the analysis revealed that China faces several challenges that impact the pace and extent of integration of AI in its pharmaceutical industry. These challenges include a lack of standardized data, a shortage of skilled labor or professionals, and data and privacy concerns. In addition, the research provides three case studies that focused on f XtalPi-AI-Enhanced Drug Discover, BioMap: Accelerating Drug Development Through AI and iCarbonX: AI-Driven Precision Medicine and provided a comprehensive analysis of how these firms have used AI to stimulate their drug discovery process. The study also provides policies that can help improve the integration of AI in the pharmaceutical and drug delivery process. [ABSTRACT FROM AUTHOR]

In December 2019, an outbreak of a respiratory disease called the coronavirus disease 2019 (COVID-19) caused by a new coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in Wuhan, China. The SARS-CoV-2, an encapsulated positive-stranded RNA virus, spread worldwide with disastrous consequences for people's health, economies, and quality of life. The disease has had far-reaching impacts on society, including economic disruption, school closures, and increased stress and anxiety. It has also highlighted disparities in healthcare access and outcomes, with marginalized communities disproportionately affected by the SARS-CoV-2. The symptoms of COVID-19 range from mild to severe. There is presently no effective cure. Nevertheless, significant progress has been made in developing COVID-19 vaccine for different therapeutic targets. For instance, scientists developed multifold vaccine candidates shortly after the COVID-19 outbreak after Pfizer and AstraZeneca discovered the initial COVID-19 vaccines. These vaccines reduce disease spread, severity, and mortality. The addition of rapid diagnostics to microscopy for COVID-19 diagnosis has proven crucial. Our review provides a thorough overview of the historical development of COVID-19 and molecular and biochemical characterization of the SARS-CoV-2. We highlight the potential contributions from insect and plant sources as anti-SARS-CoV-2 and present directions for future research. [ABSTRACT FROM AUTHOR]

With the emergence of innovative technologies, including combinatorial chemistry, high‐throughput screening, computer‐aided drug design (CADD), artificial intelligence (AI) and big data, the importance of drug design in the field of drug discovery and development is increasing. Additionally, education in drug design plays an important role in the training of pharmaceutical talent. Starting with undergraduates, cultivating pharmaceutical design thinking, developing innovation and creativity, and establishing an interdisciplinary knowledge system will not only provide students with a solid knowledge basis but also promote the development of the pharmaceutical industry in China. This article presents the current status of pharmaceutical education and the distribution of drug design courses in China and summarizes the employment prospects of graduates, thus providing valuable references and evidence for global pharmaceutical design education. [ABSTRACT FROM AUTHOR]

Drugs that cure COVID-19 have been marketed; however, this disease continues to ravage the world without becoming extinct, and thus, drug discoveries are still relevant. Since Mpro has known advantages as a drug target, such as the conserved nature of the active site and the absence of homologous proteins in the body, it receives the attention of many researchers. Meanwhile, the role of traditional Chinese medicine (TCM) in the control of epidemics in China has also led to a focus on natural products, with the hope of finding some promising lead molecules through screening. In this study, we selected a commercial library of 2526 natural products from plants, animals and microorganisms with known biological activity for drug discovery, which had previously been reported for compound screening of the SARS CoV-2 S protein, but had not been tested on Mpro. This library contains compounds from a variety of Chinese herbs, including Lonicerae Japonicae Flos, Forsythiae Fructus and Scutellariae Radix, which are derived from traditional Chinese medicine prescriptions that have been shown to be effective against COVID-19. We used the conventional FRET method for the initial screening. After two rounds of selection, the remaining 86 compounds were divided into flavonoids, lipids, phenylpropanoids, phenols, quinones, alkaloids, terpenoids and steroids according to the skeleton structures, with inhibition rates greater than 70%. The top compounds in each group were selected to test the effective concentration ranges; the IC50 values were as follows: (−)–gallocatechin gallate (1.522 ± 0.126 μM), ginkgolic acid C15:1 (9.352 ± 0.531 μM), hematoxylin (1.025 ± 0.042 μM), fraxetin (2.486 ± 0.178 μM), wedelolactone (1.003 ± 0.238 μM), hydroxytyrosol acetate (3.850 ± 0.576 μM), vanitiolide (2.837 ± 0.225 μM), β,β–dimethylacrylalkannin (2.731 ± 0.308 μM), melanin (7.373 ± 0.368 μM) and cholesteryl sodium sulfate (2.741 ± 0.234μM). In the next step, we employed two biophysical techniques, SPR and nanoDSF, to obtain KD/Kobs values: hematoxylin (0.7 μM), (−)–gallocatechin gallate (126 μM), ginkgolic acid C15:1 (227 μM), wedelolactone (0.9770 μM), β,β–dimethylacrylalkannin (1.9004 μM,), cholesteryl sodium sulfate (7.5950 μM) and melanin (11.5667 μM), which allowed better assessments of the binding levels. Here, seven compounds were the winners. Then, molecular docking experiments were specially performed by AutoDock Vina to analyze the mode of interactions within Mpro and ligands. We finally formulated the present in silico study to predict pharmacokinetic parameters as well as drug-like properties, which is presumably the step that tells humans whether the compounds are drug-like or not. Moreover, hematoxylin, melanin, wedelolactone, β,β–dimethylacrylalkannin and cholesteryl sodium sulfate are in full compliance with the "Lipinski" principle and possess reasonable ADME/T properties, they have a greater potential of being lead compounds. The proposed five compounds are also the first to be found to have potential inhibitory effects on SARS CoV-2 Mpro. We hope that the results in this manuscript may serve as benchmarks for the above potentials. [ABSTRACT FROM AUTHOR]

Radix bupleuri is one of the bulk medicinal materials in China and it is widely adopted in clinical applications and drug discovery. The investigation of agronomic traits, active component content and genetic diversity in diverse Radix bupleuri germplasms may provide evidence to promote the selection of better strains. In this research, 13 germplasms from various sources were used to investigate the variations between different Radix bupleuri germplasms. Nine biological characteristics were noted in the field, and the levels of the two primary active ingredients were determined using high performance liquid chromatography (HPLC). Moreover, the molecular marker technique of inter-simple sequence repeat (ISSR) and the unweighted pair group method with arithmetic means (UPGMA) were employed to evaluate the molecular genetic diversity. The findings showed that there was a wide range of variation among the many varieties of Radix bupleuri, with coefficients of variation for agronomic traits and active component content ranging from 7.62% to 41.54% and 36.47% to 53.70%, respectively. Moreover, there are different degrees of relationship between the two. Since there was a significant correlation between root weight and saikosaponin content, it was possible to classify a plant based on its weight and anticipate its saikosaponin content. The 13 species were divided into four groups based on their germplasm by genetic markers-based cluster analysis. This indicated the possibility that the component content would not necessarily be related to germplasm and might easily be influenced by environmental factors. The use of ISSR marker technology made it possible to precisely identify the various Radix bupleuri provenances and its counterfeit products. There may be a way to prevent the misunderstandings caused by the appearance and composition of Chinese medicinal substances. In our study, the germplasm of Radix bupleuri that was widely circulated in the market was comprehensively evaluated in terms of agronomic traits, active components and molecular level, and identified by simple means, to provide a theoretical basis for the evaluation and screening of fine germplasms of Radix bupleuri. [ABSTRACT FROM AUTHOR]

Coronavirus Disease 2019 (COVID-19) has been an unprecedented disaster for people around the world. A point particularly worth noting is that herbal medicines have made great contributions to the prevention and treatment of COVID-19 in China. Angiotensin converting enzyme 2 (ACE2) has been identified as the critical functional receptor for SARS-CoV-2. It can bind to the receptorbinding domain (RBD) of the spike protein (S protein), which is responsible for the entry of the coronavirus into host cells. Therefore, ACE2 can be regarded as an important intervention target for COVID-19. Recently, many herbal medicines have exhibited a high affinity for ACE2 in treating COVID-19. The current work summarized these herbal medicines including formulas (such as Lianhua Qingwen capsules, Xuebijing injection, Qingfei Paidu Decoction, Huashi Baidu formula, Shufeng Jiedu capsules, and Maxing Shigan decoction), single herbs including Ephedra sinica Stapf (Mahuang), Scutellariae radix (Huangqin), Lonicera japonica (Jinyinhua), and Houttuynia cordata (Yuxingcao), and active ingredients (such as ursodeoxycholic acid, glycyrrhizic acid, glycyrrhizin, salvianolic acid, quercetin, and andrographidine C), which have exhibited a high affinity for ACE2 in treating COVID-19. We hope this work may provide meaningful and useful information on further research to investigate the mechanisms of herbal medicines against SARS-CoV-2 and follow-up drug discovery. [ABSTRACT FROM AUTHOR]

In the past decade, biopharmaceutical research and development in China has been notably boosted by government policies, regulatory initiatives and increasing investments in life sciences. With regulatory agency acting as a strong driver, model-informed drug development (MIDD) is transitioning rapidly from an academic pursuit to a critical component of innovative drug discovery and development within the country. In this article, we provided a cross-sectional summary on the current status of MIDD implementations across early and late-stage drug development in China, illustrated by case examples. We also shared insights into regulatory policy development and decision-making. Various modeling and simulation approaches were presented across a range of applications. Furthermore, the challenges and opportunities of MIDD in China were discussed and compared with other regions where these practices have a more established history. Through this analysis, we highlighted the potential of MIDD to enhance drug development efficiency and effectiveness in China's evolving pharmaceutical landscape., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yuzhu Wang is a staff of Center for Drug Evaluation, National Medicine Products Administration. Jia Ji is an employee of Johnson & Johnson and holds the stocks of Johnson & Johnson. Ye Yao, Yehua Xie and Gailing Li were employees of Certara (Shanghai) Pharmaceutical Consulting Co., Ltd. Jing Nie is an employee of Abbisko Therapeutics Co., Ltd. Fengbo Xie is an associate professor at North University of China.., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Synthetic Biology, as an emerging discipline, has gained widespread attention and is developing rapidly, profoundly impacting the fields of life sciences and biotechnology. Concurrently, as emerging engineering education programs take shape, accelerated cultivation of multifaceted innovative talents represents a new mission and imperative for higher education in China. In the context of the flourishing development of Synthetic Biology, East China University of Science and Technology has established a curriculum cluster in Synthetic Biology, focusing on microbiological drug discovery and biomanufacturing. The teaching team initially reviewed the curriculum system related to Synthetic Biology and its upstream and downstream courses. Subsequently, they expanded the core courses in Synthetic Biology, creating a curriculum cluster that encompasses not only the theoretical foundations and cutting-edge technologies but also integrates with related disciplines. Moreover, the curriculum cluster leverages lectures from renowned domestic and international professors in the State Key Laboratory of Bioreactor Engineering, and harnesses the rich resources of the Program of Introducing Talents of Discipline to Universities (the "111 plan"), aiming to enhance students' innovation capabilities. With the support of this curriculum cluster and teaching team, undergraduate students actively participate in international Synthetic Biology competitions like international genetic engineering machine competition (iGEM), consistently achieving gold awards. Furthermore, many students have applied for patents and made contributions to research paper publications. This work stands as a valuable exemplar for cultivating multifaceted talents with exceptional innovative capabilities.

The unprecedented novel coronavirus disease 2019 (COVID‐19) pandemic is a threat to global health and the economy. Since the outbreak of COVID‐19, great effort has been made to reposition existing drugs to shorten development timelines, in addition to vaccine development and drug discovery campaigns. Umifenovir is a broad‐spectrum antiviral agent used to treat influenza in China and Russia and is currently undergoing clinical trials for the treatment of COVID‐19. In this article, the synthesis of umifenovir analogues and their biological evaluation are reported. The inhibitory activities of analogues against the binding of the spike glycoprotein (S‐protein) of the novel severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) to the ACE2 receptor, which is a possible mode of action for umifenovir to inhibit viral infection, were investigated. [ABSTRACT FROM AUTHOR]

Recently, advances in organoid technology have opened new avenues for the development of novel models of human cancer. Patient-derived tumor organoids retain phenotypes such as histopathological, genetic and molecular features of the original tumor. The generation of cancer, more closer to the real pathophysiological status organoids from primary patient material enables a range of therapeutic agents to be tested in the resulting organoid cultures that not only can be an excellent and innovative platform for drug discovery, but also through sensitivity test of the drug candidates can predict patient response to therapy, thereby holding great promise for personalized medicine. However, compared to traditional biobanks, living biobanks from patient-derived organoids requires stricter quality control and higher level of technical standards. With further research of organoids, a variety of solid tumors have been covered. Organoid technology was named technology of the year in life sciences in 2017. There is no quality control standard for the construction, identification and drug-screening applications of patient-derived cancer organoids in China, and there is also a lack of experts consensus for drug sensitivity test to guide precise tumor treatment. Therefore, based on the advances of patient-derived tumor organoids at home and abroad in the precision medicine, the Multidisciplinary Diagnosis and Treatment Professional Committee of China Anti-cancer Association and the Tumor Endocrinology Professional Committee of China Anticancer Association have formulated "Chinese experts consensus on quality control standards for tumor organoids diagnosis and treatment platform (2022 version)", which improves the understanding of Chinese clinicians and medical researchers on organoids' drug sensitivity test, standardizes the quality of tumor organoids diagnosis and treatment platform, and guide its clinical application in the domestic precision medicine. This consensus will be regularly updated based on the further research on organoids. [ABSTRACT FROM AUTHOR]

Covering up to 2022 Gossypol is a polyphenolic compound isolated from cottonseed. There are two optical enantiomers of gossypol, (−)-gossypol and (+)-gossypol. Gossypol exists as three different tautomers, aldehyde, ketone and lactol. Gossypol is toxic and provides a protective mechanism for cotton plants against pests. Gossypol was used as a male contraceptive in China in the 1970s. It was eventually abandoned due to noticeable side effects, disruption of potassium uptake and incomplete reversibility. Gossypol has gained considerable research interest due to its attractive biological activities, especially antitumor and antivirus. Gossypol derivatives are prepared by a structural modification to reduce toxicity and improve their therapeutic effect. This review depicts the bioactivity and regulation mechanisms of gossypol and its derivatives as drug lead compounds, with emphasis on its antitumor mechanism. The design and synthesis of pharmacologically active derivatives based on the structure of gossypol, such as gossypol Schiff bases, apogossypol, gossypolone, are thoroughly discussed. This review aims to serve as a reference for gossypol-based drug discovery and drug design. [ABSTRACT FROM AUTHOR]

The emergence of the novel coronavirus (SARS-CoV-2) that emanated from Wuhan in China in 2019 has become a global concern. The current situation warrants ethnomedicinal drug discovery and development for delivery of phytomedicines with potential for the treatment of COVID-19. The aim of this review is to provide a detailed evaluation of available information on plant species used in African traditional medicines with antiviral, anti-inflammatory, immunomodulatory, and COVID-19 symptoms relieving effects. Literature from scientific databases such as Scopus, PubMed, Google scholar, African Journals OnLine (AJOL), Science Direct, and Web of Science were used for this review. A total of 35 of the 38 reviewed plants demonstrated a wide range of antiviral activities. Bryophyllum pinnatum, Aframomum melegueta, Garcinia kola, Sphenocentrum jollyanum, Adansonia digitata, Sutherlandia frutescens, Hibiscus sabdariffa, Moringa oleifera, and Nigella sativa possess a combination of antiviral, immunomodulatory, anti-inflammatory, and COVID-19 symptoms relieving activities. Nine, 13, and 10 of the plants representing 23.7%, 34.2%, and 26.3% of the plants studied had antiviral activity with 3 other activities, antiviral activity with 2 other activities, and antiviral with one pharmacological activity alone, respectively. The plants studied were reported to be relatively safe at the subchronic toxicity level, except for 2. The study provides baseline information on the pharmacological activities, toxicity, and chemical components of 9 African medicinal plants with antiviral, immunomodulatory, anti-inflammatory, and symptoms relieving activities, thereby making the plants candidates for further investigation for effectiveness against COVID-19. [ABSTRACT FROM AUTHOR]

Chinese medicine is a national treasure that has been passed down for thousands of years in China. According to the statistics of the World Health Organization, there are currently four billion people in the world who use Chinese medicine to treat diseases, accounting for 80% of the world's total population. However, the obscurity of its theory, its unmanageable quality, its complex compositions, and the unknown effective substances and mechanisms are great obstacles to the internationalization of Chinese medicine. Here, we propose a new strategy for the development of Chinese medicine: the clinical prescription (C)-protein (P)-small-molecule (S)-disease (D) strategy, namely the CPSD strategy. The strategy uses clinical prescriptions as the source of medicine and uses computer simulation technology to find small-molecule drugs targeting therapeutic proteins for treating specific diseases so as to deepen awareness of the value of Chinese medicine. At the same time, this article takes cardiovascular drug development as an example to introduce the application of CPSD, which will be instrumental in the further development, modernization, and internationalization of Chinese medicine. [ABSTRACT FROM AUTHOR]

Cancer is a leading cause of death worldwide. The burden of cancer incidence and mortality is increasing rapidly. New approaches to cancer prevention and treatment are urgently needed. Natural products are reliable and powerful sources for anticancer drug discovery. Baicalin and baicalein, two major flavones isolated from Scutellaria baicalensis Georgi, a multi-purpose traditional medicinal plant in China, exhibit anticancer activities against multiple cancers. Of note, these phytochemicals exhibit extremely low toxicity to normal cells. Besides their cytotoxic and cytostatic activities toward diverse tumor cells, recent studies demonstrated that baicalin and baicalein modulate a variety of tumor stromal cells and extracellular matrix (ECM) in the tumor microenvironment (TME), which is essential for tumorigenesis, cancer progression and metastasis. In this review, we summarize the therapeutic potential and the mechanism of action of baicalin and baicalein in the regulation of tumor microenvironmental immune cells, endothelial cells, fibroblasts, and ECM that reshape the TME and cancer signaling, leading to inhibition of tumor angiogenesis, progression, and metastasis. In addition, we discuss the biotransformation pathways of baicalin and baicalein, related therapeutic challenges and the future research directions to improve their bioavailability and clinical anticancer applications. Recent advances of baicalin and baicalein warrant their continued study as important natural ways for cancer interception and therapy. [Display omitted] • Natural products are reliable and powerful sources for cancer drug discovery. • Baicalin and baicalein are two major flavones isolated from Scutellaria baicalensis Georgi. • Baicalin and baicalein exhibit anticancer activities against multiple cancers with extremely low toxicity to normal cells. • Baicalin and baicalein modulate tumor stromal cells and extracellular matrix in the tumor microenvironment. • Future research needs to reveal TID and improve the bioavailability for clinical applications of baicalin and baicalein. [ABSTRACT FROM AUTHOR]

Liver cancer is among the leading causes of cancer-related death worldwide and China accounts for nearly half of the global burden of liver cancer. Effective interventions such as hepatitis vaccinations, new blood tests and imaging tests significantly decreased the incidence worldwide, especially in China. Unraveling the systemic and molecular mechanisms of liver cancer would contribute to develop more effective therapies to prolong the 5 year survival of the patients. The Chinese funding agencies have been paying high attention to the basic and translational research of liver cancer. Over the last decade, the National Natural Science Foundation of China (NSFC) initiated a panel of research programs which supported liver cancer research in multiple directions. Besides, great progress has been made in basic and clinical research, platform construction and drug development in the field of liver cancer. In this article, we summarized the funding landscape, research progress, cooperation among countries and institutions, and drug discovery in China, with an attempt to compare the status and outcome with our peers globally. • This paper comprehensively assessed NSFC-funded liver cancer research projects spanning 2009-2020, offering insights into research trends in China. • This paper categorized liver cancer research areas using NSFC's application codes for 2009-2020, offering valuable guidance to researchers seeking research funding. • This is the first study that summarized liver cancer research hotspots, progress, and drug development in China, with an attempt to compare achievements with the United States and Europe. [ABSTRACT FROM AUTHOR]

The ongoing COVID-19 pandemic has resulted in millions of deaths globally, highlighting the need to develop potent prophylactic and therapeutic strategies against SARS-CoV-2. Small molecule inhibitors (remdesivir, Paxlovid, and molnupiravir) are essential complements to vaccines and play important roles in clinical treatment of SARS-CoV-2. Many advances have been made in development of anti-SARS-CoV-2 inhibitors in China, but progress in discovery and characterization of pharmacological activity, antiviral mechanisms, and clinical efficacy are limited. We review development of small molecule anti-SARS-CoV-2 drugs (azvudine [approved by the NMPA of China on July 25, 2022], VV116 [approved by the NMPA of China on January 29, 2023], FB2001, WPV01, pentarlandir, and cepharanthine) in China and summarize their pharmacological activity, potential mechanisms of action, clinical trials and use, and important milestones in their discovery. The role of structural biology in drug development is also reviewed. Future studies should focus on development of diverse second-generation inhibitors with excellent oral bioavailability, superior plasma half-life, increased antiviral activity against SARS-CoV-2 and its variants, high target specificity, minimal side effects, reduced drug-drug interactions, and improved lung histopathology. [Display omitted] • Azvudine—The first Chinese oral SARS-CoV-2 RdRp inhibitor. • VV116—China's first up-and-coming deuterated oral SARS-CoV-2 RdRp candidate. • FB2001—China's first inhaled aerosolized SARS-CoV-2 Mpro candidate drug. • Cepharanthine—Natural product-derived SARS-CoV-2 receptor binding inhibitor. • Summarize pharmacological activity, potential mechanisms of action, clinical trials, and important milestones in drug discovery. [ABSTRACT FROM AUTHOR]

The application of immune checkpoint inhibitors and FGFR protein tyrosine kinase inhibitors have made a tremendous breakthrough in bladder cancer therapy. However, inadequate drug responses and drug resistance interfere with successful treatment outcomes. For a new drug to enter the market, there is a long development cycle with high costs and low success rates. Repurposing previously Food and Drug Administration (FDA)-approved medications and using novel drug discovery strategies may be an optimal approach. Homoharringtonine (HHT) has been used for hematologic malignancies for over 40 years in China and was approved by the FDA approximately 10 years ago. Many studies have demonstrated that HHT effectively inhibits the development of several types of solid tumors, although the underlying mechanisms of action are unclear. In this study, we investigated the mechanisms underlying HHT activity against bladder cancer growth. We first compared HTT with the drugs currently used clinically for bladder cancer treatment. HHT showed stronger inhibitory activity than cisplatin, carboplatin, and doxorubicin. Our in vitro and in vivo data demonstrated that HHT inhibited proliferation, colony formation, migration, and cell adhesion of bladder cancer cells and induced apoptosis and cell cycle arrest in the nanomolar concentration range. Furthermore, we revealed that HHT treatment could downregulate the MAPK/Erk and PI3k/Akt signaling pathways by inactivating the integrin α5/β1-FAK/Src axis. HHT-induced activity reduced cell-ECM interactions and cell migration, thus suppressing tumor metastasis progression. Altogether, HHT shows enormous potential as an anticancer agent and may be applied as a combination treatment strategy for bladder cancer. [Display omitted] [ABSTRACT FROM AUTHOR]

Novel drug discovery from the active ingredients of traditional Chinese medicine is the most distinctive feature and advantageous field of China, which has provided an unprecedented opportunity. However, there are still problems such as unclear functional substance basis, action targets and mechanism, which greatly hinder the clinical transformation of active ingredients in traditional Chinese medicine. Based on the analysis of the current status and progress of innovative drug research and development in China, this paper aimed to explore the prospect and difficulties of the development of natural active ingredients from traditional Chinese medicine, and to explore the efficient discovery of trace active ingredients in traditional Chinese medicine, and obtain drug candidates with novel chemical structure, unique target/mechanism and independent intellectual property rights, in order to provide a new strategy and a new model for the development of natural medicine with Chinese characteristics.

Proteolysis targeting chimera (PROTAC) technology, one of the targeted protein degradation technologies, has drawn marked attention from researchers of both academia and industry in recent years. After over two decades of development, the literature on it has proliferated. In order to better grasp the frontiers and hot spots of PROTAC, this bibliometric analysis was carried out. The articles and reviews regarding PROTAC were culled from the Web of Science Core Collection. General information and the trend of publication outputs, countries/regions, authors, journals, influential papers, and keywords in this field were visually analyzed using CtieSpace, VOSviewer, or Excel software. As a result, a total of 808 publications were included. The number of papers regarding PROTAC significantly increased yearly. These papers mainly come from 45 countries/regions led by the USA and China. 3886 authors were identified participating in these studies, among which Craig M. Crews had the most significant number and influential articles. Journal of Medicinal Chemistry and European Journal of Medicinal Chemistry are the two journals with the most papers. After analysis, the most influential papers were identified in the area, including highly cited papers, references with citation burst, and high co-citated papers. The most common keywords including cancer, E3 ligase, drug discovery, epigenetic, resistance, and so on, represent the current and developing areas of study. BRDs, androgen receptor (AR), HDACs, estrogen receptor (ER), EGFR, CDKs, and KRAS are the most common targets. At last, frontiers and challenges of PROTAC were discussed through the bibliometric analysis. This paper will be helpful for better understanding the frontiers and hotspots of PROTAC. [Display omitted] • The first bibliometric analysis of PROTAC. • The literature information of PROTAC was visually analyzed. • Highlight the influential papers. • Highlight the PROTACs for the most common targets. [ABSTRACT FROM AUTHOR]

• New hydrazide derivative was synthesized and characterized by X-ray diffraction. • The contributions for the crystal packing were determined with Hirshfeld surface. • Molecular properties, NBO, FMO analysis were theoretically investigated using DFT method. • In-silico assays were performed regarding the new hydrazide ligand towards COVID-19 proteins. • This study provided a useful reference for the design, development, and screening of novel drug discovery. In the fall of 2019, a new type of coronavirus took place in Wuhan city, China, and rapidly spread across the world and urges the scientific community to develop antiviral therapeutic agents. In our effort we have synthesized a new hydrazide derivative, (E)- N' -(1-(4-bromophenyl)ethylidene)-2-(6-methoxynaphthalen-2-yl)propanehydrazide for this purpose because of its potential inhibitory proprieties. The asymmetric unit of the title molecule consists of two independent molecules differing noticeably in conformation. In the crystal, the independent molecules are linked by N—H···O and C—H···O hydrogen bonds and C—H···π(ring) interactions into helical chains extending along the b-axis direction. The chains are further joined by additional C—H···π(ring) interactions into the full 3-D structure. To obtain a structure-activity relationship, the DFT-NBO analysis is performed to study the intrinsic electronic properties of the title compound. Molecular modeling studies were also conducted to examine the binding affinity of the compound for the SARS-CoV-2 main protease enzyme and to determine intermolecular binding interactions. The compound revealed a stable binding mode at the enzyme active pocket with a binding energy value of -8.1 kcal/mol. Further, stable dynamics were revealed for the enzyme-compound complex and reported highly favorable binding energies. The net MMGBSA binding energy of the complex is -37.41 kcal/mol while the net MMPBSA binding energy is -40.5 kcal/mol. Overall, the compound disclosed the strongest bond of ing the main protease enzyme and might be a good lead for further structural optimization. [ABSTRACT FROM AUTHOR]

Anticancer drug discovery has yielded unprecedented progress in recent decades, resulting in the approval of innovative treatment options for patients and the successful implementation of personalized medicine in clinical practice. This remarkable progress has also reshaped the research scope of pharmacological research. This article, as a tribute to cancer research at Shanghai Institute of Materia Medica in celebration of the institute's 90th birthday, provides an overview of the conceptual revolution occurring in anticancer therapy, and summarizes our recent progress in the development of molecularly targeted therapeutics and exploration of new strategies in personalized medicine. With this review, we hope to provide a glimpse into how antitumor pharmacological researchers have embraced the new era of personalized medicine research and to propose a future path for anticancer drug discovery and pharmacological research., (© 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Inhibitors of cystic fibrosis transmembrane conductance regulator (CFTR) have been widely used for characterizing CFTR function in epithelial fluid transport and in diseases such as secretory diarrhea, polycystic kidney disease and cystic fibrosis. Few small molecule CFTR inhibitors have been discovered so far from combinatorial compound library. In the present study, we used a high throughput screening (HTS)-based natural product discovery strategy to identify new CFTR inhibitors from Chinese medicinal herbs. By screening 40,000 small molecule fractions from 500 herbal plants, we identified 42 positive fractions from 5 herbs and isolated two compounds that inhibited CFTR conductance from Chinese wild grapevine (Vitis amurensis Rupr). Mass spectrometry (MS) and nuclear magnetic resonance (NMR) studies determined the two active compounds as trans-ε-viniferin (TV) and r-2-viniferin (RV), respectively. Both compounds dose-dependently blocked CFTR-mediated iodide influx with IC50 around 20 μM. Further analysis by excised inside-out patch-clamp indicated strong inhibition of protein kinase A (PKA)-activated CFTR chloride currents by TV and RV. In ex vivo studies, TV and RV inhibited CFTR-mediated short-circuit Cl− currents in isolated rat colonic mucosa in a dose-dependent manner. In a closed-loop mouse model, intraluminal applications of TV (2.5 μg) and RV (4.5 μg) significantly reduced cholera toxin–induced intestinal fluid secretion. The present study identified two resveratrol oligomers as new CFTR inhibitors and validates our high-throughput screening method for discovery of bioactive compounds from natural products with complex chemical ingredients such as herbal plants. [ABSTRACT FROM AUTHOR]

Artemisinin, qinghaosu, was extracted from the traditional Chinese medical drug qinghao (the blue-green herb) in the early 1970s. Its ‘discovery’ can thus be hailed as an achievement of research groups who were paradoxically successful, working as they were at the height of a political mass movement in communist China, known in the West as the Cultural Revolution (1966–1976), a period that was marked by chaos, cruelty and enormous suffering, particularly, but by no means only, among the intelligentsia. On the one hand, China’s cultural heritage was seen as a hindrance to progress and Mao set out to destroy it, but on the other hand he praised it as a ‘treasure house’, full of gems that, if adjusted to the demands of contemporary society, could be used ‘for serving the people’ ( wei renmin fuwu). The success of the ‘task of combating malaria’ ( kang nüe ren wu), sometimes known as ‘task number five hundred and twenty-three’, depended crucially on modern scientists who took seriously knowledge that was recorded in a traditional Chinese medical text, Emergency Prescriptions Kept up one’s Sleeve by the famous physician Ge Hong (284–363). [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19). It emerged from China in December 2019 and rapidly spread across the globe, causing a pandemic with unprecedented impacts on public health and economy. Therefore, there is an urgent need for the development of curative treatments and vaccines. In humans, COVID-19 pathogenesis shows a wide range of symptoms, from asymptomatic to severe pneumonia. Identifying animal models of SARS-CoV-2 infection that reflect the clinical symptoms of COVID-19 is of critical importance. Nonhuman primates (NHPss) correspond to relevant models to assess vaccine and antiviral effectiveness. This review discusses the use of NHPs as models for COVID-19 research, with focus on the pathogenesis of SARS-CoV-2 infection, drug discovery and pre-clinical evaluation of vaccine candidates. [ABSTRACT FROM AUTHOR]

• Fenoterol and dobutamine inhibit SARS-CoV-2 main protease (6W63). • Docking study showed that fenoterol docked better than dobutamine. • Fenoterol and dobutamine may be used in treatment of COVID-19. • These compounds were extracted from ZINC database against COVID-19. • Virtual screening approach helped to find two FDA approved drugs. Global health is under heavy threat by a worldwide pandemic caused by a new type of coronavirus (COVID-19) since its rapid spread in China in 2019 [1]. Currently, there are no approved specific drugs and effective treatment for COVID-19 infection, but several available drugs are known to facilitate tentative treatment. Since drug design, development and testing procedures are time-consuming [2–5] , virtual screening studies with the aid of available drug databases take the initiative at this point and save the time. Besides, drug repurposing strategies promises to identify new agents for the novel diseases in a time-critical fashion. In this study, we used structure based virtual screening method on FDA approved drugs and compounds in clinical trials. As a result of this study we choose three most prominent compounds for further studies. Here we show that these three compounds (dobutamine and its two derivatives) can be considered as promising inhibitors for SARS-CoV-2 main protease and results also demonstrate the possible interactions of dobutamine and its derivatives with SARS-CoV-2 main protease (6W63) [6]. Our efforts in this work directly address current urgency of a new drug discovery against COVID-19. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Metabolomics can be used to study complex mixtures of natural products, or secondary metabolites, for many different purposes. One productive application of metabolomics that has emerged in recent years is the guiding direction for isolating molecules with structural novelty through analysis of untargeted LC-MS/MS data. The metabolomics-driven investigation and bioassay-guided fractionation of a biomass assemblage from the South China Sea dominated by a marine filamentous cyanobacteria, cf. Neolyngbya sp., has led to the discovery of a natural product in this study, wenchangamide A ( 1 ). Wenchangamide A was found to concentration-dependently cause fast-onset apoptosis in HCT116 human colon cancer cells in vitro (24 h IC 50 = 38 μM). Untargeted metabolomics, by way of MS/MS molecular networking, was used further to generate a structural proposal for a new natural product analogue of 1 , here coined wenchangamide B, which was present in the organic extract and bioactive sub-fractions of the biomass examined. The wenchangamides are of interest for anticancer drug discovery, and the characterization of these molecules will facilitate the future discovery of related natural products and development of synthetic analogues.

Coronavirus disease-2019 (COVID-19), associated with the outbreak of deadly virus originating in Wuhan, China, is now a global health emergency and a matter of serious concern. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is rapidly spreading worldwide, and WHO declared the outbreak of this disease a pandemic on March 11, 2020. Though some of the countries have succeeded in slowing down the rate of the spread of this pandemic, most the countries across the globe are still continuing to experience an increasing trend in the growth and spread of this deadly disease. Hence, in the current scenario, is has now become essential to control and finally irradicate this deadly disease using an effective vaccine. One can expect the prominent role of already available antivirals, antibodies and anti-inflammatory drugs in the market, in this pandemic. Immunomodulatory and biological therapeutics are also in the high expectations to combat COVID-19. RNA based vaccines might be more advantageous over traditional vaccines, to deal with the pandemic threat. Aiming towards this direction, clinical trials for SARS-CoV-2 vaccine are currently underway all across the globe. Currently, about 150 health related organizations and research labs are in the progress for the evolution of COVID-19 vaccines, globally. The initial aim of these clinical trials is to assess vaccine's safety, which is tested in Phase I/II/III studies where the primary outcomes typically examine the frequency of adverse effects. The vaccine is about to undergo phase III testing in several countries such as India, USA, South Africa, Brazil and England. US Government, under Operation Wrap Speed is even ready to sponsor three candidates, namely-The University of Oxford and AstraZeneca's AZD1222; Moderna's mRNA-1273; and Pfizer and BioNTech's BNT162 for Phase III trials., (Copyright © 2021. Published by Elsevier Ltd.)

Fructus Aurantii is a traditional medicated diet in East Asia. To determine the underlying chemical markers responsible for the quality and efficacy of Fructus Aurantii, a sensitive metabolomic method was applied to distinguish Fructus Aurantii in Jiangxi Province from other two geographical locations (Hunan Province and Chongqing City) in China. In the present study, multivariate analyses were adopted to compare chemical compositions in 21 batches of Fructus Aurantii samples. Among three geographical origins, 23 differential compounds were structurally identified. Serum pharmacochemistry exhibited that 22 components could be detected in rat serum. Six differential and absorbed components were selected as six potential markers. Statistical analysis revealed that the content of six markers varied widely in three origins of Fructus Aurantii. Six differential and absorbed components were evaluated further by biological activity. Neohesperidin, naringin, and meranzin showed inhibitory effect on acetylcholinesterase that regulates gastrointestinal motility in vitro and in silico, suggesting that these three components may be determined as the active biomarkers of Fructus Aurantii. These findings demonstrate the potential of biomarkers for identification and quality control of Fructus Aurantii., (© 2021 Wiley-VCH GmbH.)

Traditional Chinese medicines played an important role in the treatment of COVID-19 in 2020. Ephedra sinica, one of the major constituent herbs of multi-component herbal formula, has been widely used to treat COVID-19 in China. However, its active components are still unclear. The objectives of this study are to screen and evaluate active components from the traditional Chinese medicine Ephedra sinica for the treatment of COVID-19. In our study, we established an ACE2/CMC bioaffinity chromatography model, and then developed an ACE2/CMC-HPLC-IT-TOF-MS system for the active compounds screening and identification from Ephedra sinica extract. We performed molecular docking and surface plasmon resonance (SPR) assays to assess the binding characteristics (binding mode and K D value). We used CCK-8 staining to assess the toxicity of screened compounds, and also used SARS-CoV-2 pseudovirus to observe the viropexis effect of screened compounds in ACE2 h cells. In this current work, one fraction was fished out, separated and identified as ephedrine (EP), pseudoephedrine (PEP), and methylephedrine (MEP). Binding assays showed that the three compounds could bind with ACE2 in a special way to some amino acid residues, similar to the way SARS-CoV-2 bound with ACE2. Additionally, the three compounds, especially EP, can inhibit the entrance of SARS-CoV-2 spike pseudovirus into ACE2 h cells because they can reduce the entrance ratio of pseudovirus in the pseudovirus model. Overall, the ACE2/CMC-HPLC-IT-TOF-MS system was established and verified to be suitable for ACE2-targeted bioactive compound screening. EP, PEP, and MEP with ACE2-binding features were screened out from Ephedra sinica, and acted as blockers inhibiting SARS-CoV-2 spike pseudovirus entering ACE2 h cells.

The study on plant natural products not only helps us understand that their structural diversity is the inevitable result of plant species diversity, but also helps us understand certain rules and unity of the inevitable connection between the two. The diversity and complexity of chemical structures of many natural products are beyond imagination before we elucidated their structures. The question that follows is what is the biological significance of these natural products. Intrigued by the relationship between plant resources, natural products and biological functions, the Hao laboratory has taken an integrative approach that employs tools and knowledge from multi-disciplines, including natural product chemistry, chemical ecology and chemical biology, to unveil the effects of plant natural products on plant resistance to diseases, and environmental acclimations. Collaborating with cell biologists, the research has resulted in discovery of new mechanisms of cellular signaling and lead compounds.

Background: In 2020, the world has struggled to deal with coronavirus disease 2019 (COVID-19), which started in 2019 in China and has spread throughout the globe, affecting at least 31,175,835 humans globally and claiming 962,634 lives reported till 22nd September, 2020 by the World Health Organization. The main causative agent for this disease is known as severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). So far, there is no cure or proven therapeutics available till date. Therefore, we undertook this study to find the most probable drug candidate through a bioinformatics study. Methods: Thus, we virtually screened the Zinc natural database using HTVS tool through molecular docking studies to analyze molecules recommended for the treatment of COVID-19. Results: Ramipril benzyl ester, propafenone dimer and Lariciresinol are three important drugs found from the present study due to their medicinal application which could be helpful in treating the disease. Stylopine, quillaic acid, cinobufagin, vitisinol C, segetalin A, scopolamine, 3-oxo glycyrrhetinic acid, conchinone B, lactimidomycin and cardinalins 4 are the other lead molecules that could be used as therapeutics against COVID-19 disease. Conclusions: The studied molecules could act as an effective inhibitory drug against COVID-19., Competing Interests: No competing interests were disclosed., (Copyright: © 2020 Singh S and Florez H.)