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Small nucleic acid drugs mainly include small interfering RNA(siRNA), antisense oligonucleotide(ASO), microRNA(miRNA), messenger RNA(mRNA), nucleic acid aptamer(aptamer), and so on. Its translation or regulation can be inhibited by binding to the RNA of the target molecule. Due to its strong specificity, persistence, and curability, small nucleic acid drugs have received considerable attention in recent years. Recent studies have shown that some miRNAs from animal and plant sources can stably exist in the blood, tissue, and organs of animals and human beings and exert pharmacological action by regulating the expression of various target proteins. This paper summarized the discovery of small nucleic acids derived from traditional Chinese medicine(TCM) and natural drugs and their cross-border regulatory mechanisms and discussed the technical challenges and regulatory issues brought by this new drug, which can provide new ideas and methods for explaining the complex mechanism of TCM, developing new drugs of small nucleic acids from TCM and natural medicine, and conducting regulatory scientific research.

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Artificial intelligence (AI) is progressively spreading through the world of health, particularly in the field of oncology. AI offers new, exciting perspectives in drug development as toxicity and efficacy can be predicted from computer-designed active molecular structures. AI-based in silico clinical trials are still at their inception in oncology but their wider use is eagerly awaited as they should markedly reduce durations and costs. Health authorities cannot neglect this new paradigm in drug development and should take the requisite measures to include AI as a new pillar in conducting clinical research in oncology.

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Arrhythmia is one of the commonly heart diseases with observed abnormal heart-beat rhythm that caused by the obstacles of cardiac activity and conduction. The arrhythmic pathogenesis is complex and capricious and related with other cardiovascular diseases that may lead to heart failure and sudden death. In particular, calcium overload is recognized as the main reason causing arrhythmia through inducing apoptosis in cardiomyocytes. Moreover, calcium channel blockers have been widely used as the routine drugs for the treatment of arrhythmia, but the different arrhythmic complications and adverse effects limit their further applications and demand new drug discovery. Natural products have always been the rich minerals for the development of new drugs that could be employed as the versatile player for the discovery of safe and effective anti-arrhythmia drugs with new mechanisms. In this review, we summarized natural products with the activity against calcium signaling and the relevant mechanism of actions. We are expected to provide an inspiration for the pharmaceutical chemists to develop more potent calcium channel blockers for the treatment of arrhythmia.

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The design of new ligands with high affinity and specificity against the targets of interest has been a central focus in drug discovery. As one of the most commonly used methods in drug discovery, the cyclization represents a feasible strategy to identify new lead compounds by increasing structural novelty, scaffold diversity and complexity. Such strategy could also be potentially used for the follow-on drug discovery without patent infringement. In recent years, the cyclization strategy has witnessed great success in the discovery of new lead compounds against different targets for treating various diseases. Herein, we first briefly summarize the use of the cyclization strategy in the discovery of new small-molecule lead compounds, including the proteolysis targeting chimeras (PROTAC) molecules. Particularly, we focus on four main strategies including fused ring cyclization, chain cyclization, spirocyclization and macrocyclization and highlight the use of the cyclization strategy in lead generation. Finally, the challenges including the synthetic intractability, relatively poor pharmacokinetics (PK) profiles and the absence of the structural information for rational structure-based cyclization are also briefly discussed. We hope this review, not exhaustive, could provide a timely overview on the cyclization strategy for the discovery of new lead compounds.

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OBJECTIVE: To investigate the and studies of natural compounds and medicinal plants with anti-coronavirus activity. METHODS: A systematic review was performed based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Animal Research: Reporting of experiments guidelines to find data for medicinal plants and natural products effective against human coronaviruses in or studies. Studies published up to September 6, 2020 were included. Studies ( or ) reporting the effect of medicinal plants and natural products or their derivatives on human coronavirus were included RESULTS: Promising anti-coronavirus effects are seen with different herbal compounds like some diterpenoids, sesquiterpenoids, and three compounds in tea with 3CLpro inhibiting effect of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV); Hirsutenone, Six cinnamic amides and bavachinin are PLpro inhibitors and Tanshinones are active on both 3CLpro and PLpro. Some flavonoid compounds of Citrus fruits act on Immun-oregulation and target angiotensin-converting enzyme 2 which is used by SARS-COV for entry. Virus helicase is possibly inhibited by two compounds myricetin and scutellarein. CONCLUSION: This review shows that complementary medicine have the potential for new drug discovery against coronavirus. Further research is needed before definitive conclusions can be made concerning the safety and efficacy of the use of these medicinal plants.

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The coronavirus disease-2019 (COVID-19) pandemic started in early 2020 with the outbreak of a highly pathogenic human coronavirus. The world is facing a challenge and there is a pressing need for efficient drugs. Plants and natural compounds are a proven rich resource for new drug discovery. Considering the potential of natural products to manage the pandemic, this article was designed to provide an inclusive map of the stages and pathogenetic mechanisms for effective natural products on COVID-19. New drug discovery for the COVID-19 pandemic can encompass both prevention and disease management strategies. Preventive mechanisms that may be considered include boosting the immune response and hand hygiene in the preexposure phase; and blocking of virus binding and entry in the postexposure phase. Potential therapeutic target mechanisms include virus-directed therapies and host-directed therapies. Several medicinal plants and natural products, such as Withania somnifera (L.) Dunal and propolis for prevention; Tanacetum parthenium (L.) for treatment; and Ammoides verticillata (Desf.) Briq and Nigella sativa L. for both prevention and treatment have been found effective and are good targets for future research. The examples of phytochemical compounds that may be effective include aloin and terpenes as anti-septics; isothymol, dithymoquinone, and glycyrrhizin as inhibitors of virus binding and entry; glycyrrhizin, and berberine as replication suppressants; ginsenoside Rg1 and parthenolide as immunomodulators; and eriocitrin, rhoifolin, hesperidin, naringin, rutin, and veronicastroside as anti-complements. Recognizing different mechanisms of fighting against this virus can lead to a more systematic approach in finding natural products and medicinal plants for COVID-19 prevention and treatment.

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With antimicrobial resistance creating a major public health crisis, the designing of novel antimicrobial compounds that effectively combat bacterial infection is becoming increasingly critical. Interdisciplinary approaches integrate the best features of whole-cell phenotypic evaluation to validate novel therapeutic targets and discover new leads to combat antimicrobial resistance. In this project, whole-cell phenotypic evaluation such as testing inhibitors on bacterial growth, viability, efflux pump, biofilm formation and their interaction with other drugs were performed on a panel of Gram-positive, Gram-negative and acid-fast group of bacterial species. This enabled additional antimicrobial activities of compounds belonging to the flavonoid family including ketones, chalcones and stilbenes, to be identified. Flavonoids have received renewed attention in literature over the past decade, and a variety of beneficial effects of these compounds have been illuminated, including anti-cancer, anti-inflammatory, anti-tumour as well as anti-fungal and anti-bacterial. However, their mechanisms of action are yet to be identified. In this paper, we found that the compounds belonging to the flavonoid family exerted a range of anti-infective properties being identified as novel efflux pump inhibitors, whilst offering the opportunity to be used in combination therapy. The compound 2-phenylacetophenone displayed broad-spectrum efflux pump inhibition activity, whilst trans-chalcone, displayed potent activity against Gram-negative and mycobacterial efflux pumps causing inhibition higher than known potent efflux pump inhibitors, verapamil and chlorpromazine. Drug-drug interaction studies also highlighted that 2-phenylacetophenone not only has the potential to work additively with known antibacterial agents that affect the cell-wall and DNA replication but also trans-chalcone has the potential to work synergistically with anti-tubercular agents. Overall, this paper shows how whole-cell phenotypic analysis allows for the discovery of new antimicrobial agents and their consequent mode of action whilst offering the opportunity for compounds to be repurposed, in order to contribute in the fight against antimicrobial resistance.

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Diabetes mellitus, one of the most common endocrine-metabolic disorders, has caused significant morbidity and mortality worldwide. To avoid sugar digestion and postprandial hyperglycemia, it is necessary to inhibit α-glucosidase, a digestive enzyme with an important role in carbohydrate digestion. The criteria for the selection of alkaloids are based on their in vitro and in vivo activities on glucose modulation. The current study assessed the bonding potential of isolated alkaloids with the targeted protein. For this purpose, the 3D structure of the target protein (α-glucosidase) was reproduced using MODELLER 9.20. The modeled 3D structure was then validated and confirmed by using the RAMPAGE, ERRAT, and Verify3D online servers. The molecular docking of 32 alkaloids reported as α-glucosidase inhibitors, along with reference compounds (acarbose and miglitol), was done through MOE-Dock applied in MOE software to predict the binding modes of these drug-like compounds. The results revealed that nummularine-R and vindoline possess striking interactions with active site residues of the target protein, and were analogous to reference ligands. In conclusion, the current study provided a computational background to the α-glucosidase inhibitors tested. This novel information should facilitate the development of new and effective therapeutic compounds for the treatment of diabetes mellitus.

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Diabetic nephropathy(DN) is a kind of severe diabetes mellitus(DM) complications,which is one of the most common cause of end-stage renal failure.The incidence of DN increases with the increase of the number of DM patients,and early prevention is the key.DM and DN are characteristic advantages of Tibetan medicine,the "holistic view" of dynamic balance based on the three major factors in the body(Sanyin,included rlung,mkhris-pa and bad-gan) is a unique understanding of DM and DN among Tibetan medical practitioners,and which has rich and unique clinical and medication experiences in DN treatment.This paper discussed the medical theory "holistic view" on the Tibetan medicine for DM and DN,dug commonly used Tibetan drugs and Tibetan medical prescriptions for clinical treatment of DN,in order to provide new ideas for the treatment of DN and the discovery of new drugs for DN, and give full play to the unique advantages of Tibetan medicine.

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The traditional efficacy of traditional Chinese medicine (TCM) is to summarize the clinical efficacy of TCM under the guidance of TCM theory,and it possess important guiding significance for the clinical use of TCM.Comparing with the modern medical system,the TCM system was different from western medicine in diagnosis and treatment modes,and the disease targets of TCM maybe more extensive than that of western medicine.Based on the traditional efficacy of TCM,combined with modern means of science and technology,the research on material basis and pharmacological mechanism of TCM was beneficial to discovery the new targets,new mechanism,new material and the secondary development of new drug of TCM.Furthermore,it also has far-reaching significance on interpret the modern scientific connotation of TCM efficacy.Therefore,deriving from the traditional efficacy of TCM,the research of modern pharmacodynamic material basis is the source for original research.

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Alzheimer disease (AD), the most common dementia, is a chronic, progressive and neuro-degenerative disorder. With an increasing prevalence, AD has been the third cause of death after cardio-vascular diseases and cancer in the elderly population. However, the pathogenesis of AD remains unclear, which has led to a fairly slow development of drugs for AD and a dim view of future treatments of AD. It has been a hot spot and a big challenge to develop effective, therapeutic drugs for AD. Recently, this topic was discussed via WeChat by experts from the Neuropsychiatric WeChat Group, which consists of 300 Chinese-origin neuroscientists and neuropsychiatrists in China or overseas. The experts pointed out the problems that might have misled researches on drug discovery, such as the misleading but dominating AD pathology hypotheses and problems with the platforms for drug screening. Therefore, it is important to review the pathology of AD and the treatment strategies from big data and the overall view of the disease, which may shed new light on AD therapy to develop drugs for multiple targets, leading to omni-direc-tional, comprehensive treatments of AD. The development of AD can be further classified into different stages based on the upstream factors of AD pathology. Interestingly, it has been found that the AD brain has mitochondria damage and dysfunction; long-term exposure to low doses of ionizing radiation can also cause AD-like pathological changes. These provide novel views and ideas in terms of the path-ological process and preventive and therapeutic strategies for AD.

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Microorganisms have provided abundant sources of natural products, which have been developed as commercial products for human medicine, animal health, and plant crop protection. Avermectin discovered from Streptomyces avermectinius was the first macrocyclic lactones against parasitic worms. The semi-synthetic derivative of avermectin, ivermectin, was used to treat onchocerciasis and lymphatic filariasis in human. Two scientists were awarded the Nobel Prize for the great contribution to the discovery and research of these drugs. This paper reviewed the study and development of avermectins and ivermectin. This is one of the series papers about historical story on natural medicinal chemistry.

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Ginger is a commonly used spice and herbal medicine worldwide. Besides its extensive use as a condiment, ginger has been used in traditional Chinese medicine for the management of various medical conditions. In recent years, ginger has received wide attention due to its observed antiemetic and anticancer activities. This paper reviews the potential role of ginger and its active constituents in cancer chemoprevention. The phytochemistry, bioactivity, and molecular targets of ginger constituents, especially 6-shogaol, are discussed. The content of 6-shogaol is very low in fresh ginger, but significantly higher after steaming. With reported anti-cancer activities, 6-shogaol can be served as a lead compound for new drug discovery. The lead compound derivative synthesis, bioactivity evaluation, and computational docking provide a promising opportunity to identify novel anticancer compounds originating from ginger.

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Tuberculosis (TB) poses a grave predicament to the world as it is not merely a scientific challenge but a socio-economic burden as well. A prime cause of mortality in human due to an infectious disease; the malady and its cause, Mycobacterium tuberculosis have remained an enigma with many questions that remain unanswered. The ability of the pathogen to survive and switch between varied physiological states necessitates a protracted therapeutic regimen that exerts an excessive strain on low-resource countries. To complicate things further, there has been a significant rise of antimicrobial resistance. Existing control measures, including treatment regimens have remained fairly uniform globally for at least half a century and require reinvention. Overcoming the societal and scientific challenges requires an increase in dialog to identify key regions that need attention and effective partners with whom successful collaborations can be fostered. In this report, we explore the discussions held at the International TB Summit 2015 hosted by EuroSciCon, which served as an excellent platform for researchers to share their recent findings. Ground-breaking results require outreach to affect policy design, governance and control of the disease. Hence, we feel it is important that meetings such as these reach a wider, global audience.

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Hair color is affected not only by genetic, age, and environmental factors, but also by the regulation of many cytokines and proteins. The generation of melanin is mainly regulated by POMC, α-MSH, MC1R, MITF, tyrosinase, TRP-1, TRP-2, ASIP, etc. Hair color anomaly is often considered to be a feature of aging which brings great psychological pressure to the people, but the treartment by relevant drugs is still blank. This article summarizes the effect target and the function ways of those natural medicines with great efficacy on the treatment of hair graying. This review may provide some theoretical basis for the application of natural medicines in the treatment of hair graying.

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Network pharmacology is an emerging discipline based on the Disease-Gene-Drug multilevel network. And it has been used to forecast the drug targets and improve the efficiency of drug discovery. Its research ideas are similar to the overall efficacy of traditional Chinese medicine (TCM), which attracts more and more medical re-searchers to look for the joint point of TCM and network pharmacology. A series of approaches on disease-related genes, predicting the information of target and active ingredients of TCM emerge. In this paper, the network pharma-cology research tools, databases and their applications were summarized and introduced. This paper also proposed scientific strategies to separate active ingredients of TCM using network pharmacology, so as to improve the efficiency and speed of finding active ingredients of TCM.

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Natural medicines play an important role in keeping the healthy of human beings from past till now. Recently, the importance of natural medicines in research and development of new drugs has been attracted the attention of scientists. The research and development of anti-aging drugs from natural products have captured more and more attention. In this paper, the historical story on the discovery and study of the famous natural anti-aging drug-ginkgolides is summarized in memory of the great discoveries and in honor of the scientists so as to provide the reference for future related research.