Frontiers in drug discovery最新文献_第4页

Novel mesothelin antibodies enable crystallography of the intact mesothelin ectodomain and engineering of potent, T cell-engaging bispecific therapeutics 新型间皮素抗体使完整间皮素外畴的晶体学和有效的工程T细胞参与双特异性治疗成为可能

Frontiers in drug discovery Pub Date : 2023-08-03 DOI: 10.3389/fddsv.2023.1216516

I-Yen Lin, P. Rupert, K. Pilat, Raymond O. Ruff, D. Friend, M. Chan, Midori Clarke, B. Hoffstrom, Jane Carter, S. Meshinchi, A. Bandaranayake, C. Mehlin, James M. Olson, R. Strong, C. Correnti

{"title":"Novel mesothelin antibodies enable crystallography of the intact mesothelin ectodomain and engineering of potent, T cell-engaging bispecific therapeutics","authors":"I-Yen Lin, P. Rupert, K. Pilat, Raymond O. Ruff, D. Friend, M. Chan, Midori Clarke, B. Hoffstrom, Jane Carter, S. Meshinchi, A. Bandaranayake, C. Mehlin, James M. Olson, R. Strong, C. Correnti","doi":"10.3389/fddsv.2023.1216516","DOIUrl":"https://doi.org/10.3389/fddsv.2023.1216516","url":null,"abstract":"Mesothelin is a glypiated, cell-surface glycoprotein expressed at low levels on normal mesothelium but overexpressed by many cancers. Implicated in cell adhesion and multiple signaling pathways, mesothelin’s precise biological function and overall structure remain undefined. Antibodies targeting mesothelin have been engineered into immunotoxins, antibody-drug conjugates, CAR-T cells, or bispecific T cell engagers as candidate therapeutics but most face challenges, including binding epitopes that are not optimal for selected modalities. Here we describe the isolation and characterization of a novel anti-mesothelin antibody, 1A12, including crystallographic mapping of the 1A12 epitope in relation to other antibodies (amatuximab, anetumab). 1A12 possesses uniquely favorable properties, including a membrane-proximal epitope, and enabled structure determination of the complete mesothelin ectodomain. We incorporated 1A12 into two different bispecific T cell engaging architectures with various anti-CD3 co-targeting elements as candidate therapeutics, demonstrating in vitro functionality and potency.","PeriodicalId":73080,"journal":{"name":"Frontiers in drug discovery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45451457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The importance of good practices and false hits for QSAR-driven virtual screening real application: a SARS-CoV-2 main protease (Mpro) case study qsar驱动的虚拟筛选实际应用中良好实践和错误命中的重要性:SARS-CoV-2主蛋白酶(Mpro)案例研究

Frontiers in drug discovery Pub Date : 2023-07-25 DOI: 10.3389/fddsv.2023.1237655

M. Serafim, S. Q. Pantaleão, E. B. da Silva, J. McKerrow, A. O’Donoghue, B. E. Mota, K. M. Honório, V. Maltarollo

{"title":"The importance of good practices and false hits for QSAR-driven virtual screening real application: a SARS-CoV-2 main protease (Mpro) case study","authors":"M. Serafim, S. Q. Pantaleão, E. B. da Silva, J. McKerrow, A. O’Donoghue, B. E. Mota, K. M. Honório, V. Maltarollo","doi":"10.3389/fddsv.2023.1237655","DOIUrl":"https://doi.org/10.3389/fddsv.2023.1237655","url":null,"abstract":"Computer-Aided Drug Design (CADD) approaches, such as those employing quantitative structure-activity relationship (QSAR) methods, are known for their ability to uncover novel data from large databases. These approaches can help alleviate the lack of biological and chemical data, but some predictions do not generate sufficient positive information to be useful for biological screenings. QSAR models are often employed to explain biological data of chemicals and to design new chemicals based on their predictions. In this review, we discuss the importance of data set size with a focus on false hits for QSAR approaches. We assess the challenges and reliability of an initial in silico strategy for the virtual screening of bioactive molecules. Lastly, we present a case study reporting a combination approach of hologram-based quantitative structure-activity relationship (HQSAR) models and random forest-based QSAR (RF-QSAR), based on the 3D structures of 25 synthetic SARS-CoV-2 Mpro inhibitors, to virtually screen new compounds for potential inhibitors of enzyme activity. In this study, optimal models were selected and employed to predict Mpro inhibitors from the database Brazilian Compound Library (BraCoLi). Twenty-four compounds were then assessed against SARS-CoV-2 Mpro at 10 µM. At the time of this study (March 2021), the availability of varied and different Mpro inhibitors that were reported definitely affected the reliability of our work. Since no hits were obtained, the data set size, parameters employed, external validations, as well as the applicability domain (AD) could be considered regarding false hits data contribution, aiming to enhance the design and discovery of new bioactive molecules.","PeriodicalId":73080,"journal":{"name":"Frontiers in drug discovery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46875160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

9-PAHSA displays a weak anti-inflammatory potential mediated by specific antagonism of chemokine G protein-coupled receptors 9-PAHSA在趋化因子G蛋白偶联受体的特异性拮抗作用下表现出微弱的抗炎潜能

Frontiers in drug discovery Pub Date : 2023-07-20 DOI: 10.3389/fddsv.2023.1138461

P. Wohlfart, Mounir Chehtane, E. Luna, R. Mehta, M. Korn, A. Konkar, U. Schwahn, S. Petry, N. Tennagels, M. Bielohuby

{"title":"9-PAHSA displays a weak anti-inflammatory potential mediated by specific antagonism of chemokine G protein-coupled receptors","authors":"P. Wohlfart, Mounir Chehtane, E. Luna, R. Mehta, M. Korn, A. Konkar, U. Schwahn, S. Petry, N. Tennagels, M. Bielohuby","doi":"10.3389/fddsv.2023.1138461","DOIUrl":"https://doi.org/10.3389/fddsv.2023.1138461","url":null,"abstract":"Introduction: 9-PAHSA belongs to a class of endogenous mammalian bioactive lipids, fatty acid esters of hydroxy fatty acids (FAHFA), that are present in circulation at nanomolar concentrations in mice and humans. Published preclinical data suggest beneficial effects of 9-PAHSA treatment on glucose metabolism as well as modulation of immune function. However, receptor molecules with high affinity towards these lipids have not been identified so far.Methods: In a broad screen of a panel of G protein-coupled receptors (GPCRs) we discovered that 9-PAHSA displays antagonist activity with an IC50 in the micromolar range on selected chemokine receptors, namely, CCR6, CCR7, CXCR4, and CXCR5. The potential immunomodulatory activities in a human cellular model of innate immunity were then investigated.Results and discussion: In our in vitro experiments, a weak anti-inflammatory potential for high concentrations of 9-PAHSA (10–100 µM) could be detected, as treatment reduced the LPS-induced secretion of certain chemokines, such as CXCL10, MIP-1 beta and MCP. Regarding metabolic effects, we re-investigated 9-PAHSA on glucose metabolism and insulin sensitivity in vitro and in mice confirming conclusions from our earlier study that FAHFAs lack glucoregulatory activity following an acute treatment. In conclusion, the specific interactions with a subset of chemokine receptors may contribute to weak anti-inflammatory properties of 9-PAHSA, but further studies are needed to confirm its in anti-inflammatory potential in vivo.","PeriodicalId":73080,"journal":{"name":"Frontiers in drug discovery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47300131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting proteases and proteolytic processing of unusual N-terminal extensions of Plasmodium proteins: parasite peculiarity 疟原虫特异性的靶向蛋白酶和异常N端延伸的蛋白水解处理

Frontiers in drug discovery Pub Date : 2023-07-13 DOI: 10.3389/fddsv.2023.1223140

Ankita Tehlan, A. Saha, S. Dhar

{"title":"Targeting proteases and proteolytic processing of unusual N-terminal extensions of Plasmodium proteins: parasite peculiarity","authors":"Ankita Tehlan, A. Saha, S. Dhar","doi":"10.3389/fddsv.2023.1223140","DOIUrl":"https://doi.org/10.3389/fddsv.2023.1223140","url":null,"abstract":"More than sesquicentennial years of malarial research, however the unique malarial parasite, Plasmodium still bewilders us with its atypical characteristic features. Elimination strategies, deeper knowledge of the parasite biology and pathways can help combat this global health concern that affects ∼250 million people annually. In this review, we unveil an unusual phenomenon observed in the parasite proteome, N-terminal extensions in proteins and highlight that the proteases that may be involved in their processing events, are potential candidates to target this pathogen. Plasmodium encodes larger proteins as compared to its eukaryotic counterparts with homology regions present in the C-terminus of the protein. In contrast, the function of unusual extensions in the N-terminus remains mostly elusive. This novelty observed in Plasmodium proteins is collated here with a focus on replication proteins. The plausible functions and prevalence of these extensions, despite the reduction in genome size, through the parasite evolution are also mentioned. We hypothesize that these extensions, propagated via the energy consuming cellular processes in the otherwise host-dependent obligate parasite, are beneficial to the parasite in ways that are yet to be explored. Consequently, targeting the proteolytic processing of these proteins and the involved proteases would serve as a new drug development regimen to tackle the emerging resistance in parasites to existing antimalarials.","PeriodicalId":73080,"journal":{"name":"Frontiers in drug discovery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45716501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

FAIR data management: what does it mean for drug discovery? 公平数据管理:对药物发现意味着什么?

Frontiers in drug discovery Pub Date : 2023-07-12 DOI: 10.3389/fddsv.2023.1226727

Yojana Gadiya, V. Ioannidis, David Henderson, P. Gribbon, P. Rocca-Serra, V. Satagopam, Susanna-Assunta Sansone, Wei Gu

{"title":"FAIR data management: what does it mean for drug discovery?","authors":"Yojana Gadiya, V. Ioannidis, David Henderson, P. Gribbon, P. Rocca-Serra, V. Satagopam, Susanna-Assunta Sansone, Wei Gu","doi":"10.3389/fddsv.2023.1226727","DOIUrl":"https://doi.org/10.3389/fddsv.2023.1226727","url":null,"abstract":"The drug discovery community faces high costs in bringing safe and effective medicines to market, in part due to the rising volume and complexity of data which must be generated during the research and development process. Fully utilising these expensively created experimental and computational data resources has become a key aim of scientists due to the clear imperative to leverage the power of artificial intelligence (AI) and machine learning-based analyses to solve the complex problems inherent in drug discovery. In turn, AI methods heavily rely on the quantity, quality, consistency, and scope of underlying training data. While pre-existing preclinical and clinical data cannot fully replace the need for de novo data generation in a project, having access to relevant historical data represents a valuable asset, as its reuse can reduce the need to perform similar experiments, therefore avoiding a “reinventing the wheel” scenario. Unfortunately, most suitable data resources are often archived within institutes, companies, or individual research groups and hence unavailable to the wider community. Hence, enabling the data to be Findable, Accessible, Interoperable, and Reusable (FAIR) is crucial for the wider community of drug discovery and development scientists to learn from the work performed and utilise the findings to enhance comprehension of their own research outcomes. In this mini-review, we elucidate the utility of FAIR data management across the drug discovery pipeline and assess the impact such FAIR data has made on the drug development process.","PeriodicalId":73080,"journal":{"name":"Frontiers in drug discovery","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42341615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The tumor suppressor 5A2, a synthetic miR-7-5p mimic, targets oncogenic and metabolic pathways, as revealed by transcriptome-wide analysis 全转录组分析显示，肿瘤抑制因子5A2是一种合成的miR-7-5p模拟物，靶向致癌和代谢途径

Frontiers in drug discovery Pub Date : 2023-07-07 DOI: 10.3389/fddsv.2023.1181637

Marion T. J. van den Bosch, Bryony J. Telford, S. Yahyanejad, Thijs de Gunst, Harm C. den Boer, R. Vos, C. Duurland, R. Biemans, L. Dubois, L. V. van Pinxteren, R. Schaapveld, M. Janicot

{"title":"The tumor suppressor 5A2, a synthetic miR-7-5p mimic, targets oncogenic and metabolic pathways, as revealed by transcriptome-wide analysis","authors":"Marion T. J. van den Bosch, Bryony J. Telford, S. Yahyanejad, Thijs de Gunst, Harm C. den Boer, R. Vos, C. Duurland, R. Biemans, L. Dubois, L. V. van Pinxteren, R. Schaapveld, M. Janicot","doi":"10.3389/fddsv.2023.1181637","DOIUrl":"https://doi.org/10.3389/fddsv.2023.1181637","url":null,"abstract":"As cancer is a multifactorial disease, the multimodal action of microRNAs makes them an attractive tool for novel therapeutic approaches. The tumor suppressive miR-7-5p has been shown to act on many aspects of oncogenesis, including cell proliferation, migration and angiogenesis, by targeting a spectrum of key genes. We developed a synthetic chemically modified miR-7-5p mimic, 5A2, and performed a comprehensive functional characterization in a panel of human cancer cell lines. 5A2 reduced cell proliferation in most cell lines by inducing cell cycle arrest. To enable systemic delivery of 5A2 to tumors, it was formulated in a novel lipid nanoparticle (INT-5A2) and we demonstrated the anti-tumor activity of INT-5A2 in an experimental human liver tumor-bearing mouse model. Next, RNA-sequencing was used to gain more insight into the molecular mechanism of action of 5A2 and demonstrated a broad repression of target mRNAs. Interestingly, Ingenuity Pathway Analysis revealed a new role for 5A2 in metabolic pathways. Validation experiments in vitro showed that 5A2 reduced the expression of key glycolysis and glutaminolysis enzymes, leading to a decrease in glycolysis, lactate secretion and intracellular glutamate availability. Taken together, these data strongly suggest that miR-7-5p/5A2 is a potent tumor suppressor that targets various key cellular pathways across cancer types. Therefore, 5A2 may represent a promising novel treatment strategy in oncology.","PeriodicalId":73080,"journal":{"name":"Frontiers in drug discovery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43596813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Yin-yang in drug discovery: rethinking de novo design and development of predictive models 药物发现中的阴阳：重新思考预测模型的从头设计和开发

Frontiers in drug discovery Pub Date : 2023-06-21 DOI: 10.3389/fddsv.2023.1222655

Ana L. Chávez‐Hernández, E. López-López, J. Medina‐Franco

{"title":"Yin-yang in drug discovery: rethinking de novo design and development of predictive models","authors":"Ana L. Chávez‐Hernández, E. López-López, J. Medina‐Franco","doi":"10.3389/fddsv.2023.1222655","DOIUrl":"https://doi.org/10.3389/fddsv.2023.1222655","url":null,"abstract":"Chemical and biological data are the cornerstone of modern drug discovery programs. Finding qualitative yet better quantitative relationships between chemical structures and biological activity has been long pursued in medicinal chemistry and drug discovery. With the rapid increase and deployment of the predictive machine and deep learning methods, as well as the renewed interest in the de novo design of compound libraries to enlarge the medicinally relevant chemical space, the balance between quantity and quality of data are becoming a central point in the discussion of the type of data sets needed. Although there is a general notion that the more data, the better, it is also true that its quality is crucial despite the size of the data itself. Furthermore, the active versus inactive compounds ratio balance is also a major consideration. This review discusses the most common public data sets currently used as benchmarks to develop predictive and classification models used in de novo design. We point out the need to continue disclosing inactive compounds and negative data in peer-reviewed publications and public repositories and promote the balance between the positive (Yang) and negative (Yin) bioactivity data. We emphasize the importance of reconsidering drug discovery initiatives regarding both the utilization and classification of data.","PeriodicalId":73080,"journal":{"name":"Frontiers in drug discovery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47887205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MMV006087 is a potent Malaria Box compound against Plasmodium falciparum clinical parasites MMV006087是一种有效的抗恶性疟原虫临床寄生虫的疟疾箱化合物

Frontiers in drug discovery Pub Date : 2023-06-15 DOI: 10.3389/fddsv.2023.1190471

J. Chirawurah, Bridget Adikah, F. Ansah, E. Laryea-Akrong, Harry Danwonno, C. Morang’a, Daniel Dosoo, L. Amenga-Etego, G. Awandare, Y. Aniweh

{"title":"MMV006087 is a potent Malaria Box compound against Plasmodium falciparum clinical parasites","authors":"J. Chirawurah, Bridget Adikah, F. Ansah, E. Laryea-Akrong, Harry Danwonno, C. Morang’a, Daniel Dosoo, L. Amenga-Etego, G. Awandare, Y. Aniweh","doi":"10.3389/fddsv.2023.1190471","DOIUrl":"https://doi.org/10.3389/fddsv.2023.1190471","url":null,"abstract":"The emergence of drug-resistant malaria parasites to artemisinin and its partner drugs highlights the need to increase the arsenal of new antimalarials with novel mechanisms of action. To help achieve this aim, this study tested the potency of three Malaria Box compounds (MMV006087, MMV085203, and MMV008956) against five laboratory strains and twenty clinical isolates of Plasmodium falciparum using optimized in vitro growth inhibitory assays. The results were compared to the response from four standard antimalarials-artesunate, chloroquine, mefloquine, and halofantrine. From the results, MMV006087 was the most potent compound with an average IC50 of 22.13 nM compared to MMV085203 (average IC50 of 137.90 nM) and MMV008956 (average IC50 of 262.30 nM). On average, the laboratory strains were also less susceptible to the three Malaria Box compounds (average IC50 of 162.30 nM) compared to the clinical isolates (average IC50 of 135.40 nM). Additionally, MMV006087 was less potent than artesunate but twice more efficacious than chloroquine against the laboratory strains and clinical isolates. The data from this study validate the potency of MMV006087 and MMV085203 as promising antimalarials worthy of further exploration. This study further substantiates the need to include clinical isolates in antimalarial compound screening activities.","PeriodicalId":73080,"journal":{"name":"Frontiers in drug discovery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45937320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lessons that can be learned from the SARS-CoV-2 pandemic and their impact on the prophylaxis and treatment development for neglected tropical arboviruses 从严重急性呼吸系统综合征冠状病毒2型大流行中可以吸取的教训及其对被忽视的热带虫媒病毒预防和治疗发展的影响

Frontiers in drug discovery Pub Date : 2023-06-01 DOI: 10.3389/fddsv.2023.1176768

Danilo Rosa-Nunes, Danilo B. M. Lucchi, Robert Andreata-Santos, L. Janini, C. Braconi

{"title":"Lessons that can be learned from the SARS-CoV-2 pandemic and their impact on the prophylaxis and treatment development for neglected tropical arboviruses","authors":"Danilo Rosa-Nunes, Danilo B. M. Lucchi, Robert Andreata-Santos, L. Janini, C. Braconi","doi":"10.3389/fddsv.2023.1176768","DOIUrl":"https://doi.org/10.3389/fddsv.2023.1176768","url":null,"abstract":"In the 21st Century, emergence and re-emergence of infectious diseases is significant and has an increasing importance in global concern of public health. Based on the COVID-19 pandemic and recently reported epidemics, most human pathogens originate in zoonosis. Many of such pathogens are related to viruses that have RNA genomes, which can be presented structurally as a single-strand or double-strand. During the last two decades, a timeline of major RNA viruses emergencies can be exemplified, such as Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) in 2003, influenza A virus (H1N1) pdm09 in 2009, Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, Ebola virus (EBOV) in 2013–2016, Zika virus (ZIKV) in 2015 and the SARS-CoV-2 pdm19 in 2019. Even so, prophylactic or therapeutic drugs are unavailable for many RNA viruses circulating. Nonetheless, the COVID-19 pandemic brought considerable scientific advances in accelerating progress regarding prophylaxis, antiviral and drug development, and novel treatments. Regarding RNA virus diseases for humans, arboviruses play an essential and neglected role, constantly reemerging and affecting almost half of the human population, for which no drug has been licensed. Here we review the consolidated RNA viruses’ emergence and re-emergence in the 21st Century through available data. Then, we explored valuable lessons gained during the SARS-CoV-2 pandemic and focused on potential epidemiologic updates, prophylaxis, available treatments, and viral drug inhibitors. Finally, we explore arbovirus’s significance and the ongoing development of effective vaccines, antiviral drugs, and novel therapeutic approaches as strategies to control these neglected tropical diseases (NTD).","PeriodicalId":73080,"journal":{"name":"Frontiers in drug discovery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49066776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Drug discovery and development: introduction to the general public and patient groups 药物发现和开发:向公众和患者群体介绍

Frontiers in drug discovery Pub Date : 2023-05-24 DOI: 10.3389/fddsv.2023.1201419

Natesh Singh, P. Vayer, Shivalika Tanwar, J. Poyet, K. Tsaioun, B. Villoutreix

{"title":"Drug discovery and development: introduction to the general public and patient groups","authors":"Natesh Singh, P. Vayer, Shivalika Tanwar, J. Poyet, K. Tsaioun, B. Villoutreix","doi":"10.3389/fddsv.2023.1201419","DOIUrl":"https://doi.org/10.3389/fddsv.2023.1201419","url":null,"abstract":"Finding new drugs usually consists of five main stages: 1) a pre-discovery stage in which basic research is performed to try to understand the mechanisms leading to diseases and propose possible targets (e.g., proteins); 2) the drug discovery stage, during which scientists search for molecules (two main large families, small molecules and biologics) or other therapeutic strategies that interfere or cure the investigated disease or at least alleviate the symptoms; 3) the preclinical development stage that focuses on clarifying the mode of action of the drug candidates, investigates potential toxicity, validates efficacy on various in vitro and in vivo models, and starts evaluate formulation; 4) the clinical stage that investigates the drug candidate in humans; 5) the reviewing, approval and post-market monitoring stage during which the drug is approved or not. In practice, finding new treatments is very challenging. Despite advances in the understanding of biological systems and the development of cutting-edge technologies, the process is still long, costly with a high attrition rate. New approaches, such as artificial intelligence and novel in vitro technologies, are being used in an attempt to rationalize R&D and bring new drugs to patients faster, but several obstacles remain. Our hope is that one day, it becomes possible to rapidly design inexpensive, more specific, more effective, non-toxic, and personalized drugs. This is a goal towards which all authors of this article have devoted most of their careers. Graphical Abstract","PeriodicalId":73080,"journal":{"name":"Frontiers in drug discovery","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41899960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0