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Record W3119952098 · doi:10.1038/s41573-020-00114-z

Natural products in drug discovery: advances and opportunities

2021· review· en· W3119952098 on OpenAlexfundno aff
Atanas G. Atanasov, Sergey B. Zotchev, Verena M. Dirsch, İlkay Erdoğan Orhan, Maciej Banach, Judith M. Rollinger, Davide Barreca, Wolfram Weckwerth, Rudolf Bauer, Edward A. Bayer, Anupam Bishayee, Valery N. Bochkov, Günther K. Bonn, Nady Braidy, Franz Bučar, Alejandro Cifuentes, Grazia D’Onofrio, Michael J. Bodkin, Marc Diederich, Albena T. Dinkova‐Kostova, Thomas Efferth, Khalid El Bairi, Nicolas Arkells, Tai-Ping Fan, Bernd L. Fiebich, Michael Freissmuth, Milen I. Georgiev, Simon Gibbons, Keith M. Godfrey, Christian W. Gruber, Jag Heer, Lukas A. Huber, Elena Ibáñez, Anake Kijjoa, Anna K. Kiss, Aiping Lü, Francisco A. Macı́as, Mark J.S. Miller, Andrei Mocan, Rolf Müller, Ferdinando Nicoletti, George Perry, Valeria Pittalà, Luca Rastrelli, Michael Ristow, Gian Luigi Russo, A. Sanches‐Silva, Daniela Schuster, Helen Sheridan, Krystyna Skalicka‐Woźniak, Léandros Skaltsounis, Eduardo Sobarzo‐Sánchez, David S. Bredt, Hermann Stuppner, Nikolay Tzvetkov, Rosa Anna Vacca, Bharat B. Aggarwal, Maurizio Battino, Francesca Giampieri, Michaël Wink, Jean‐Luc Wolfender, Jianbo Xiao, Andy Wai Kan Yeung, Gérard Lizard, Michael Popp, Michael Heinrich, Marc Stadler, Maria Daglia, Robert Verpoorte, Claudiu T. Supuran

Bibliographic record

VenueNature Reviews Drug Discovery · 2021
Typereview
Languageen
FieldMedicine
TopicMicrobial Natural Products and Biosynthesis
Canadian institutionsnot available
FundersUCB PharmaEuropean Regional Development FundNarodowe Centrum Badań i RozwojuInstituto de Salud Carlos IIIEconomic and Social Research CouncilBiotechnology and Biological Sciences Research CouncilNational Institute on Minority Health and Health DisparitiesEuropean CommissionEngineering and Physical Sciences Research CouncilTürkiye Bilimler AkademisiServierMedical Research CouncilÖsterreichische ForschungsförderungsgesellschaftDirectorate for Biological SciencesEsperion TherapeuticsNestecUniwersytet Medyczny w LublinieEen Häerz fir kriibskrank KannerNational Institute on AgingAlexander von Humboldt-StiftungAbbott VascularUnitatea Executiva pentru Finantarea Invatamantului Superior, a Cercetarii, Dezvoltarii si InovariiErasmus+Ministero dell’Istruzione, dell’Università e della RicercaNational Institute for Health Research Southampton Biomedical Research CentreGazi ÜniversitesiSeoul National UniversitySchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungDeutsche ForschungsgemeinschaftTenovusDanoneDeutscher Akademischer AustauschdienstMinistério da Ciência, Tecnologia e Ensino SuperiorAmgenRecherches Scientifiques LuxembourgAustrian Science FundNational Institute for Health and Care ResearchNational Research FoundationCentro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y NutriciónUniversität InnsbruckChina Scholarship CouncilBundesministerium für Bildung und ForschungCancer Research UKNational Institutes of HealthMylanMinisterio de Ciencia, Innovación y UniversidadesHong Kong Baptist UniversityNational Science FoundationBayer Consumer HealthRobert J. Kleberg, Jr. and Helen C. Kleberg FoundationUniversität WienValeant Pharmaceuticals InternationalSanofiDeutsches KrebsforschungszentrumEli Lilly and CompanyFundação para a Ciência e a TecnologiaPfizer
KeywordsDrug discoveryIsolation (microbiology)Risk analysis (engineering)Pharmaceutical industryNatural (archaeology)Natural productBiotechnologyData scienceBiochemical engineeringComputer scienceBusinessEngineeringBiologyBioinformatics

Abstract

fetched live from OpenAlex

Natural products and their structural analogues have historically made a major contribution to pharmacotherapy, especially for cancer and infectious diseases. Nevertheless, natural products also present challenges for drug discovery, such as technical barriers to screening, isolation, characterization and optimization, which contributed to a decline in their pursuit by the pharmaceutical industry from the 1990s onwards. In recent years, several technological and scientific developments - including improved analytical tools, genome mining and engineering strategies, and microbial culturing advances - are addressing such challenges and opening up new opportunities. Consequently, interest in natural products as drug leads is being revitalized, particularly for tackling antimicrobial resistance. Here, we summarize recent technological developments that are enabling natural product-based drug discovery, highlight selected applications and discuss key opportunities.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.005
Threshold uncertainty score0.018

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0020.001
Bibliometrics0.0030.004
Science and technology studies0.0000.001
Scholarly communication0.0020.003
Open science0.0010.001
Research integrity0.0020.003
Insufficient payload (model declined to judge)0.0050.003

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.042
GPT teacher head0.326
Teacher spread0.284 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNot applicable
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

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Citations5,001
Published2021
Admission routes1
Has abstractno

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