Assessing the reaction to and efficacy of the Screener drug discovery and development board game as a pedagogical tool in postgraduate courses

Screener, a board game supplemented with online resources, was introduced and distributed by the Brazilian Society of Pharmacology and Experimental Therapeutics to postgraduate programs as an instructional tool for the process of drug discovery and development (DDD). In this study, we provided a comprehensive analysis of five critical aspects for evaluating the quality of educational games, namely: 1) description of the intervention; 2) underlying pedagogical theory; 3) identification of local educational gaps; 4) impact on diverse stakeholders; and 5) elucidation of iterative quality enhancement processes. We also present qualitative and quantitative assessments of the effectiveness of this game in 11 postgraduate courses. We employed the MEEGA+ online survey, comprising thirty-three close-ended unipolar items with 5-point Likert-type response scales, to assess student perceptions of the quality and utility of Screener. Based on 115 responses, the results indicated a highly positive outlook among students. In addition, we performed a preliminary evaluation of learning outcomes in two courses involving 28 students. Pre- and post-quizzes were applied, each consisting of 20 True/False questions directly aligned with the game's content. The analysis revealed significant improvement in students' performance following engagement with the game, with scores rising from 8.4 to 13.3 (P<0.0001, paired t-test) and 9.7 to 12.7 (P<0.0001, paired t-test). These findings underscore the utility of Screener as an enjoyable and effective tool for facilitating a positive learning experience in the DDD process. Notably, the game can also reduce the educational disparities across different regions of our continental country.

The evolution and application progress of non-modified drug target discovery CETSA technology / 药学学报

Understanding the research methods for drug protein targets is crucial for the development of new drugs, clinical applications of drugs, drug mechanisms, and the pathogenesis of diseases. Cellular thermal shift assay (CETSA), a target research method without modification, has been widely used since its development. Now, there are various CETSA-based technology combinations, such as mass spectrometry-based cellular thermal shift assay (MS-CETSA), isothermal dose response-cellular thermal shift assay (ITDR-CETSA), amplified luminescent proximity homogeneous assay-cellular thermal shift assay (Alpha-CETSA), etc., which combine their respective advantages and further expand the application scope of CETSA. These technologies are suitable for the entire drug development chain, from drug screening to monitoring the target binding and off-target toxicity of drugs in patients. Based on the author's research experience, this paper reviews the principles of CETSA and related binding technologies, their application in target discovery, and the progress of data processing and analysis in recent years, aiming to provide reference and reference for the further application of CETSA.

Organoides de origen humano como modelo fisiopatológico de evaluación terapéutica de fármacos en COVID-19 / Organoids as a physiopathology model and therapeutic drug evaluation tool in COVID-19

Introducción: La pandemia causada por SARS-CoV-2 ha impactado al mundo gravemente en diversos ámbitos y con ello ha surgido la necesidad de contar con herramientas con mayor relevancia fisiológica para investigar patologías complejas como el COVID-19. Los organoides son un modelo experimental con características únicas como la capacidad de autoformar una estructura tridimensional utilizando células en cultivo. Sobre esta base, surge la siguiente pregunta ¿son los organoides un modelo experimental factible para reflejar la fisiopatología del COVID-19 y evaluar la eficacia de fármacos que limiten su progresión? Metodología: Para abordar esta interrogante, esta revisión plantea el analizar la validez de los organoides como modelo experimental y verificar su utilidad en la evaluación de fármacos para el COVID-19. Para cumplir estos objetivos se realizó una revisión sistemática cualitativa de la literatura, a través de una búsqueda en PubMed con el término 'COVID-19 and stem cells and organoids' y también en un número especial de la revista Cell. Resultados: Se organizaron los resultados relevantes por sistema fisiológico y en la evaluación de fármacos. Los organoides más empleados para estudios de COVID-19 correspondieron a tejido respiratorio, nervioso y digestivo. Algunos resultados encontrados en la revisión fueron similares a aquellos obtenidos a partir de tejidos de pacientes COVID-19 o autopsias, encontrándose hallazgos relevantes como la posible disrupción de la barrera epitelial del sistema nervioso por infección del plexo coroideo. También se logró observar efectividad de fármacos que posteriormente pasaron a ser aprobados y utilizados exitosamente en pacientes. Conclusión: Los organoides se pueden componer a partir de diferentes tipos celulares y bajo diferentes protocolos experimentales, siendo relevante la lectura crítica de los artículos científicos para decidir si sus resultados son extrapolables a la fisiopatología de la enfermedad.

Introduction: The pandemic caused by SARS-CoV-2 has impacted the world severely in several aspects and has created the need for research tools to study the COVID-19 disease. Organoids are experimental models with unique characteristics, like the ability to self-assemble in a tridimensional structure. Based on this, the following question arises: are organoids an experimental model suitable to reflect the physiopathology of COVID-19 and to allow the evaluation of the efficacy of drugs that limit its progression? Methods: To approach this question, this review aimed to analyze the validity of organoids as an experimental model and verify their utility in COVID-19 drug evaluation. To resolve these objectives, a qualitative systematic review was done through a PubMed search with the terms 'COVID-19 and stem cells and organoids' and on a special issue of the Cell Journal. Results: The results were organized by physiologic system and therapeutic drug evaluation. The most utilized tissues for the COVID-19 study were respiratory, nervous, and digestive. Some results found in the review were like those obtained from COVID-19 patient tissue or autopsies, finding some relevant discoveries like the possibility of the choroid plexus disruption in the nervous system caused by the infection. Efficacy was also observed in approved drugs and used later in patients successfully. Conclusion: Organoids might be composed starting with different cell types and under a variety of experimental protocols, being relevant the critical reading of the scientific literature to decide whether their results can be extrapolated to the pathophysiology of the disease

Epistemología de la investigación social / Epistemology of social research

INTRODUCCIÓN. La epistemología, rama de la filosofía que estudia el proceso de investigación y su producto el conocimiento científico, implica ámbitos de la ciencia con enfoque positivismo y postpositivismo, interpretativismo, teoría crítica; y, transcomplejo, cada uno de ellos con los elementos paradigmáticos de: ontología, epistemología y metodología, su conocimiento y aplicabilidad en los diferentes ámbitos es fundamental porque sus enfoques generan ciencia. OBJETIVO. Desarrollar capacidades intelectuales en bases contextuales y teóricas en epistemología de la investigación social, indispensables para el ejercicio profesional en el ámbito de la investigación científica y del conocimiento científico. MATERIALES Y MÉTODOS. Estudio observacional, descriptivo, con población y muestra conocida de 30 modalidades de publicación, periodo junio a julio 2020. Los criterios de inclusión fueron: fuentes secundarias de información bibliográfica validadas en el ámbito de las ciencias sociales. La técnica de observación fue en buscadores bibliográficos PUBMED, Scielo, Scopus, Diccionario de Descriptores en Ciencias de la Salud y la Real Academia Española. La tarea de revisar la literatura de investigación comprendió la identificación, selección, análisis crítico, descripción escrita, interpretación, discusión y conclusión de la información que existe sobre la epistemología de la investigación social, tema, que se registró con aplicación de un gestor de referencias bibliográficas, tipo Microsoft Word. RESULTADOS. Se logró obtener capacidades intelectuales al estructurar la cronológica de la epistemología de la investigación social, del conocimiento científico y nuevas perspectivas para el ejercicio profesional en el ámbito de la investigación científica. CONCLUSIÓN. Las perspectivas se orientan a integrar paradigmas pasados y futuros con visión de transcomplejidad, espacios organológicos de una gran red, conformación de cibercomunidades de investigación, uso de método integrador, nuevo lenguaje en equipos multidisciplinarios, agentes como el foco principal de la teoridad epistémica en espacio, tiempo y la relación entre las cosas.

INTRODUCTION. Epistemology, a branch of philosophy that studies the research process and its product, scientific knowledge, involves areas of science focussed in with positivism and postpositivism, interpretivism, critical theory; and, transcomplex, each one of them with the paradigmatic elements of: ontology, epistemology and methodology, their knowledge and applicability in the different fields is fundamental because their approaches generate science. OBJECTIVE. Develop intellectual capacities on contextual and theoretical bases in the epistemology of social research, essential for professional practice in the field of scientific research and scientific knowledge. MATERIALS AND METHODS. Observational, descriptive study, with population and a known sample of 30 publication modalities, period June to July 2020. The inclusion criteria were: secondary sources of bibliographic information validated in the field of social sciences. The observation technique was in bibliographic search engines PUBMED, Scielo, Scopus, Dictionary of Descriptors in Health Sciences and the Royal Spanish Academy. The task of reviewing the research literature included the identification, selection, critical analysis, written description, interpretation, discussion and conclusion of the information that exists on the epistemology of social research, subject, which was registered with the application of a reference manager bibliographic, Microsoft Word type. RESULTS. Intellectual capacities were obtained by structuring the chronology of the epistemology of social research, scientific knowledge and new perspectives for professional practice in the field of scientific research. CONCLUSION. The perspectives are aimed at integrating past and future paradigms with a vision of transcomplexity, organological spaces of a large network, formation of research cyber communities, use of integrative method, new language in multidisciplinary teams, agents as the main focus of epistemic theory in space, time and the relationship between things.

First-in-class small molecule drugs in 2022 / 药学学报

2022 is the third year of the global COVID-19 pandemic, and its troubles on new drug discovery are gradually apparent. 37 new drugs were approved by the FDA's Center for Drug Evaluation and Research (CDER) last year, down from the peak of 50 new drug approvals in 2021. Notably, first-in-class drugs still occupy a dominant position this year, with a total of 21 drugs. Among them, 7 are first-in-class small molecule drugs. Although the total number of new drug approvals in 2022 sharply decreased, some first-in-class small molecule drugs were regarded as significant, including mitapivat, the first oral activator targeting the pyruvate kinase (PK); mavacamten, the first selective allosteric inhibitor targeting the myocardial β myosin ATPase; deucravacitinib, the first deuterated allosteric inhibitor targeting the tyrosine kinase 2 (TYK2); and lenacapavir, the first long-acting inhibitor targeting the HIV capsid. Generally, the research of first-in-class drugs needs to focus on difficult clinical problems and can treat some specific diseases through novel targets and biological mechanisms. There are tremendous challenges in the research processes of new drugs, including biological mechanism research, target selection, molecular screening, lead compound identification and druggability optimization. Therefore, the success of first-in-class drugs development has prominent guidance significance for new drug discovery. This review briefly describes the discovery background, research and development process and therapeutic application of 3 first-in-class small molecule drugs to provide research ideas and methods for more first-in-class drugs.

Non clinical pharmacodynamic evaluation system of high-altitude hypoxic brain injury / 药学学报

The air at high altitude is thin and belongs to the environment of low temperature, low oxygen and low pressure. The human brain is the most sensitive to hypoxia. Hypoxia will cause dysfunction of the central nervous system, resulting in high-altitude hypoxic brain injury, including mild high altitude headache and more destructive high altitude cerebral edema (HACE). Recently, with more and more people work and live in high altitude areas, the development of high-altitude hypoxic brain injury drugs would produce great economic value and social significance. Non clinical pharmacodynamic evaluation is the basic of drug development, which plays a key role in improving the success rate of clinical transformation and reducing the risk of clinical research. This review summarizes the cell models and animal models, and the evaluation indicators usually used to explore the candidates of high-altitude hypoxic brain injury. We aim at establishing a standardized non clinical efficacy evaluation system for high altitude hypoxic encephalopathy, and provide a standardized reference for drug development in hypoxic encephalopathy at high altitude at nonclinical stage.

Screening methods of SARS-CoV-2 main protease inhibitors and current applications / 药学学报

COVID-19 epidemic continues to spread around the world till these days, and it is urgent to develop more safe and effective new drugs. Due to the limited P3 biosafety laboratories for directly screening inhibitors of virulent viruses with high infectivity, it is necessary to develop rapid and efficient screening methods for viral proteases and other related targets. The main protease (Mpro), which plays a key role in the replication cycle of SARS-CoV-2, is highly conserved and has no homologous proteases in humans, making it an ideal target for drug development. From two different levels, namely, molecular level and cellular level, this paper summarizes the reported screening methods of SARS-CoV-2 Mpro inhibitors through a variety of representative examples, expecting to provide references for further development of SARS-CoV-2 Mpro inhibitors.

Label-free target discovery technology of small molecule drug and its application in traditional Chinese medicines / 药学学报

The discovery of drug targets plays a crucial role in drug research. Accurate information of small molecule drug-protein interaction can be provided by label-free target discovery technology without any structural modification at the small molecule. So, the label-free drug target discovery technology had become the powerful tool to discover the targets of drugs. Due to the “multi-component and multi-target” characteristics of traditional Chinese medicines (TCMs), the research on its targets and mechanism had been restricted. Based on potential of the label-free target discovery technology in the research of TCMs, this paper summarized the label-free target discovery technology and its application in TCMs research. It will provide a reference for the discovery of targets of TCMs and a new view for promoting the modernization of TCMs.

Advances and prospects in targeted protein degradation / 药学实践杂志

Targeted protein degradation (TPD) techniques eliminate pathogenic proteins by hijacking the intracellular proteolysis machinery which includes the ubiquitin-proteasome system (UPS) and the lysosomal degradation pathway, holding promise to overcome the limitations of traditional inhibitors and further broaden the target space including many “undruggable” targets, and provide new targeted treatments for drug discovery. In this review, recent advances in a variety of promising TPD strategies were summarized, such as proteolysis targeting chimera (PROTAC), molecular glue, lysosome-targeting chimaera (LYTAC), autophagosome-tethering compound (ATTEC), autophagy-targeting chimera AUTAC and AUTOTAC, particularly. The representative case studies, potential applications and challenges were analyzed.

A novel IRAK4/PIM1 inhibitor ameliorates rheumatoid arthritis and lymphoid malignancy by blocking the TLR/MYD88-mediated NF-κB pathway

Interleukin-1 receptor-associated kinase 4 (IRAK4) is a pivotal enzyme in the Toll-like receptor (TLR)/MYD88 dependent signaling pathway, which is highly activated in rheumatoid arthritis tissues and activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL). Inflammatory responses followed by IRAK4 activation promote B-cell proliferation and aggressiveness of lymphoma. Moreover, proviral integration site for Moloney murine leukemia virus 1 (PIM1) functions as an anti-apoptotic kinase in propagation of ABC-DLBCL with ibrutinib resistance. We developed a dual IRAK4/PIM1 inhibitor KIC-0101 that potently suppresses the NF-κB pathway and proinflammatory cytokine induction in vitro and in vivo. In rheumatoid arthritis mouse models, treatment with KIC-0101 significantly ameliorated cartilage damage and inflammation. KIC-0101 inhibited the nuclear translocation of NF-κB and activation of JAK/STAT pathway in ABC-DLBCLs. In addition, KIC-0101 exhibited an anti-tumor effect on ibrutinib-resistant cells by synergistic dual suppression of TLR/MYD88-mediated NF-κB pathway and PIM1 kinase. Our results suggest that KIC-0101 is a promising drug candidate for autoimmune diseases and ibrutinib-resistant B-cell lymphomas.

Precise assembly of inside-out cell membrane camouflaged nanoparticles via bioorthogonal reactions for improving drug leads capturing

Cell membrane camouflaged nanoparticles have been widely used in the field of drug leads discovery attribute to their unique biointerface targeting function. However, random orientation of cell membrane coating does not guarantee effective and appropriate binding of drugs to specific sites, especially when applied to intracellular regions of transmembrane proteins. Bioorthogonal reactions have been rapidly developed as a specific and reliable method for cell membrane functionalization without disturbing living biosystem. Herein, inside-out cell membrane camouflaged magnetic nanoparticles (IOCMMNPs) were accurately constructed via bioorthogonal reactions to screen small molecule inhibitors targeting intracellular tyrosine kinase domain of vascular endothelial growth factor recptor-2. Azide functionalized cell membrane acted as a platform for specific covalently coupling with alkynyl functionalized magnetic Fe3O4 nanoparticles to prepare IOCMMNPs. The inside-out orientation of cell membrane was successfully verified by immunogold staining and sialic acid quantification assay. Ultimately, two compounds, senkyunolide A and ligustilidel, were successfully captured, and their potential antiproliferative activities were further testified by pharmacological experiments. It is anticipated that the proposed inside-out cell membrane coating strategy endows tremendous versatility for engineering cell membrane camouflaged nanoparticles and promotes the development of drug leads discovery platforms.

Chemistry-led investigations into the mode of action of NAMPT activators, resulting in the discovery of non-pyridyl class NAMPT activators

The cofactor nicotinamide adenine dinucleotide (NAD+) plays a key role in a wide range of physiological processes and maintaining or enhancing NAD+ levels is an established approach to enhancing healthy aging. Recently, several classes of nicotinamide phosphoribosyl transferase (NAMPT) activators have been shown to increase NAD+ levels in vitro and in vivo and to demonstrate beneficial effects in animal models. The best validated of these compounds are structurally related to known urea-type NAMPT inhibitors, however the basis for the switch from inhibitory activity to activation is not well understood. Here we report an evaluation of the structure activity relationships of NAMPT activators by designing, synthesising and testing compounds from other NAMPT ligand chemotypes and mimetics of putative phosphoribosylated adducts of known activators. The results of these studies led us to hypothesise that these activators act via a through-water interaction in the NAMPT active site, resulting in the design of the first known urea-class NAMPT activator that does not utilise a pyridine-like warhead, which shows similar or greater activity as a NAMPT activator in biochemical and cellular assays relative to known analogues.

Exploration and practice on construction of Tibetan medicine prescription information database and knowledge discovery / 中国中药杂志

This study aimed to explore the underlying framework and data characteristics of Tibetan prescription information. The information on Tibetan medicine prescriptions was collected based on 11 Tibetan medicine classics, such as Four Medical Canons(Si Bu Yi Dian). The optimal classification method was used to summarize the information structure of Tibetan medicine prescriptions and sort out the key problems and solutions in data collection, standardization, translation, and analysis. A total of 11 316 prescriptions were collected, involving 139 011 entries and 63 567 pieces of efficacy information of drugs in prescriptions. The information on Tibe-tan medicine prescriptions could be summarized into a "seven-in-one" framework of "serial number-source-name-composition-efficacy-appendix-remarks" and 18 expansion layers, which contained all information related to the inheritance, processing, origin, dosage, semantics, etc. of prescriptions. Based on the framework, this study proposed a "historical timeline" method for mining the origin of prescription inheritance, a "one body and five layers" method for formulating prescription drug specifications, a "link-split-link" method for constructing efficacy information, and an advanced algorithm suitable for the research of Tibetan prescription knowledge discovery. Tibetan medicine prescriptions have obvious characteristics and advantages under the guidance of the theories of "three factors", "five sources", and "Ro-nus-zhu-rjes" of Tibetan medicine. Based on the characteristics of Tibetan medicine prescriptions, this study proposed a multi-level and multi-attribute underlying data architecture, providing new methods and models for the construction of Tibetan medicine prescription information database and knowledge discovery and improving the consistency and interoperability of Tibetan medicine prescription information with standards at all levels, which is expected to realize the "ancient and modern connection-cleaning up the source-data sharing", so as to promote the informatization and modernization research path of Tibetan medicine prescriptions.

Emerging trends in organ-on-a-chip systems for drug screening

New drug discovery is under growing pressure to satisfy the demand from a wide range of domains, especially from the pharmaceutical industry and healthcare services. Assessment of drug efficacy and safety prior to human clinical trials is a crucial part of drug development, which deserves greater emphasis to reduce the cost and time in drug discovery. Recent advances in microfabrication and tissue engineering have given rise to organ-on-a-chip, an in vitro model capable of recapitulating human organ functions in vivo and providing insight into disease pathophysiology, which offers a potential alternative to animal models for more efficient pre-clinical screening of drug candidates. In this review, we first give a snapshot of general considerations for organ-on-a-chip device design. Then, we comprehensively review the recent advances in organ-on-a-chip for drug screening. Finally, we summarize some key challenges of the progress in this field and discuss future prospects of organ-on-a-chip development. Overall, this review highlights the new avenue that organ-on-a-chip opens for drug development, therapeutic innovation, and precision medicine.

SARS-CoV-2 spike host cell surface exposure promoted by a COPI sorting inhibitor

Via an insufficient coat protein complex I (COPI) retrieval signal, the majority of SARS-CoV-2 spike (S) is resident in host early secretory organelles and a tiny amount is leaked out in cell surface. Only surface-exposed S can be recognized by B cell receptor (BCR) or anti-S therapeutic monoclonal antibodies (mAbs) that is the trigger step for B cell activation after S mRNA vaccination or infected cell clearance by S mAbs. Now, a drug strategy to promote S host surface exposure is absent. Here, we first combined structural and biochemical analysis to characterize S COPI sorting signals. A potent S COPI sorting inhibitor was then invented, evidently capable of promoting S surface exposure and facilitating infected cell clearance by S antibody-dependent cellular cytotoxicity (ADCC). Importantly, with the inhibitor as a probe, we revealed Omicron BA.1 S is less cell surface exposed than prototypes because of a constellation of S folding mutations, possibly corresponding to its ER chaperone association. Our findings not only suggest COPI is a druggable target against COVID-19, but also highlight SARS-CoV-2 evolution mechanism driven by S folding and trafficking mutations.

Live biotherapeutic products: the forefront of innovative drug development driven by biotechnology / 生物工程学报

As human microbiome research advances, a large body of evidence shows that microorganisms are closely related to human health. Probiotics were discovered and used as foods or dietary supplements with health benefits in the last century. Microorganisms have shown broader application prospects in human health since the turn of the century, owing to the rapid development of technologies such as microbiome analysis, DNA synthesis and sequencing, and gene editing. In recent years, the concept of "next-generation probiotics" has been proposed as new drugs, and microorganisms are considered as "live biotherapeutic products (LBP)". In a nutshell, LBP is a living bacterial drug that can be used to prevent or treat certain human diseases and indications. Because of its distinct advantages, LBP has risen to the forefront of drug development research and has very broad development prospects. This review introduces the varieties and research advances on LBP from a biotechnology standpoint, followed by summarizing the challenges and opportunities for LBP clinical implementations, with the aim to facilitate LBP development.

Discovery of new Schistosoma mansoni aspartyl protease inhibitors by structure-based virtual screening

BACKGROUND Schistosomiasis is a neglected tropical disease caused by trematodes of the genus Schistosoma, with a limited treatment, mainly based on the use of praziquantel (PZQ). Currently, several aspartic proteases genes have already been identified within the genome of Schistosoma species. At least one enzyme encoded from this gene family (SmAP), named SmCD1, has been validated for the development of schistosomicidal drugs, since it has a key role in haemoglobin digestion by worms. OBJECTIVE In this work, we integrated a structure-based virtual screening campaign, enzymatic assays and adult worms ex vivo experiments aiming to discover the first classes of SmCD1 inhibitors. METHODS Initially, the 3D-structures of SmCD1, SmCD2 and SmCD3 were generated using homology modelling approach. Using these models, we prioritised 50 compounds from 20,000 compounds from ChemBridge database for further testing in adult worm aqueous extract (AWAE) and recombinant SmCD1 using enzymatic assays. FINDINGS Seven compounds were confirmed as hits and among them, two compounds representing new chemical scaffolds, named 5 and 19, had IC50 values against SmCD1 close to 100 μM while presenting binding efficiency indexes comparable to or even higher than pepstatin, a classical tight-binding peptide inhibitor of aspartyl proteases. Upon activity comparison against mammalian enzymes, compound 50 was selective and the most potent against the AWAE aspartic protease activity (IC50 = 77.7 μM). Combination of computational and experimental results indicate that compound 50 is a selective inhibitor of SmCD2. Compounds 5, 19 and 50 tested at low concentrations (10 uM) were neither cytotoxic against WSS-1 cells (48 h) nor could kill adult worms ex-vivo, although compounds 5 and 50 presented a slight decrease on female worms motility on late incubations times (48 or 72 h). MAIN CONCLUSION Overall, the inhibitors identified in this work represent promising hits for further hit-to-lead optimisation.

Progress of the development of anti-COVID-19 drugs / 药学学报

Since the outbreak of the novel coronavirus (SARS-CoV-2) disease COVID-19 (also known as 2019-nCoV) caused by SARS-CoV-2 in the end of 2019, it has spread rapidly in worldwide. Besides developing effective vaccines, it is urgent to develop safe and effective anti-SARS-CoV-2 drugs to fight this disease. Paxlovid, molnupiravir, sotrovimab and bebtelovimab are urgently authorized by FDA have been proved to be effective against Omicron. This manuscript mainly reviews the recent progress of effective inhibitors against the virus in the world, including receptor inhibitors, antibodies, natural product inhibitors, synthetic inhibitors and broad-spectrum antiviral drugs that are effective against other RNA viruses.

FBDD and drugs originated from FBDD / 药学学报

The binding of small molecule drugs to targets is mostly through non-covalent bonds, and hydrogen bond, electrostatic, hydrophobic and van der Waals interactions function to maintain the binding force. The more these binding factors lead to strong bindings and high activities. However, it is often accompanied by the increase of molecular size, resulting in pharmacokinetic problems such as membrane penetration and absorption, as well as metabolism, which ultimately affects the drug success. Fragment-based drug discovery (FBDD) is to screen high-quality fragment library to find hits. Combine with structural biology, FBDD generates lead compounds by means of fragment growth, linking and fusion, and finally drug candidates by the optimization operation. During the value chain FBDD is closely related to structure-based drug discovery (SBDD). In this paper, the principle of FBDD is briefly described by several launched drugs.

Discovery and distribution of and response to arbovirus in China over the past seven decades / 中国血吸虫病防治杂志

Arbovirus is a group of virus transmitted by blood-sucking arthropod bites, which infects both arthropods and vertebrates. More than 600 arboviruses have been characterized worldwide until now, including 65 highly pathogenic viruses, which pose a high threat to public health. The risk of arbovirus transmission is increasing due to climate change, international trade and urbanization. The review summarizes the discovery and distribution of emerging and reemerging arboviruses and novel arboviruses with potential pathogenic risks, and proposes responses to the arbovirus transmission risk, so as to provide insights into the research and management of arboviruses and arthropod-borne infectious diseases in China.