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Natural products in drug discovery: advances and opportunities

Nature Reviews Drug Discovery · 2021 · Vol. 20(3) · pp. 200–216

Atanas G. Atanasov✉(University of Vienna)Sergey B. Zotchev(University of Vienna)Verena M. Dirsch(University of Vienna)the International Natural Product Sciences Taskforce(Gazi University)İlkay Erdoğan Orhan(Polish Mother’s Memorial Hospital Research Institute)Maciej Banach(University of Vienna)Judith M. Rollinger(University of Messina)Davide Barreca(University of Vienna)Wolfram Weckwerth(University of Graz)Rudolf Bauer(Weizmann Institute of Science)Edward A. Bayer(Sami Labs (India))Shaheen Majeed(Lake Erie College of Osteopathic Medicine)Anupam Bishayee(University of Graz)Valery N. Bochkov(Universität Innsbruck)Günther K. Bonn(UNSW Sydney)Nady Braidy(University of Graz)Franz Bučar(Instituto de Investigación en Ciencias de la Alimentación)Alejandro Cifuentes(Casa Sollievo della Sofferenza)Grazia D’Onofrio(Evotec (United Kingdom))Michael J. Bodkin(Seoul National University)Marc Diederich(University of Dundee)Albena T. Dinkova‐Kostova(Johannes Gutenberg University Mainz)Thomas EfferthKhalid El BairiNicolas Arkells(University of Cambridge)Tai-Ping Fan(University of Freiburg)Bernd L. Fiebich(Medical University of Vienna)Michael Freissmuth(Bulgarian Academy of Sciences)Milen I. Georgiev(University College London)Simon Gibbons(University Hospital Southampton NHS Foundation Trust)Keith M. Godfrey(Medical University of Vienna)Christian W. Gruber(UCB Pharma (United Kingdom))Jag Heer(Innsbruck Medical University)Lukas A. Huber(Instituto de Investigación en Ciencias de la Alimentación)Elena Ibáñez(Universidade do Porto)Anake Kijjoa(Medical University of Warsaw)Anna K. Kiss(Hong Kong Baptist University)Aiping Lü(Universidad de Cádiz)Francisco A. Macı́asMark J.S. Miller(Iuliu Hațieganu University of Medicine and Pharmacy)Andrei Mocan(Helmholtz Centre for Infection Research)Rolf Müller(University of Catania)Ferdinando Nicoletti(The University of Texas at San Antonio)George Perry(University of Catania)Valeria Pittalà(University of Salerno)Luca Rastrelli(ETH Zurich)Michael Ristow(Institute of Food Science)Gian Luigi Russo(Instituto Nacional de Investigação Agrária e Veterinária)A. Sanches‐Silva(Paracelsus Medical University)Daniela Schuster(Trinity College Dublin)Helen Sheridan(Medical University of Lublin)Krystyna Skalicka‐Woźniak(National and Kapodistrian University of Athens)Léandros Skaltsounis(Universidade de Santiago de Compostela)Eduardo Sobarzo‐Sánchez(Janssen (United States))David S. Bredt(Universität Innsbruck)Hermann Stuppner(Health Research Institute of the Balearic Islands)Antonio García‐Ríos(Bulgarian Academy of Sciences)Nikolay Tzvetkov(Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies)Rosa Anna Vacca(Inflammation Research Foundation)Bharat B. Aggarwal(Marche Polytechnic University)Maurizio Battino(Marche Polytechnic University)Francesca Giampieri(Heidelberg University)Michaël Wink(University of Geneva)Jean-Luc Wolfender(Jiangsu University)Jianbo Xiao(University of Hong Kong)Andy Wai Kan Yeung(Inserm)Gérard Lizard(Bionorica (Germany))Michael Popp(University College London)Michael Heinrich(Iuliu Hațieganu University of Medicine and Pharmacy)Ioana Ilie(German Center for Infection Research)Marc Stadler(Jiangsu University)Maria Daglia(Leiden University)Robert Verpoorte✉(University of Florence)Claudiu T. Supuran(University of Florence)

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Abstract

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.

Microbial Natural Products and Biosynthesis Computational Drug Discovery Methods Phytochemical compounds biological activitiesDrug discoveryIsolation (microbiology)Risk analysis (engineering)Pharmaceutical industryNatural (archaeology)Natural productBiotechnologyData scienceBiochemical engineeringComputer science

MeSH terms

Biological ProductsCommunicable DiseasesDrug IndustryHumansNeoplasmsGenomeDrug Discovery

Funding

National Science Foundation
Amgen
Eli Lilly and Company
Pfizer
Sanofi
Alexander von Humboldt-Stiftung
Danone
Deutsches Krebsforschungszentrum
Valeant Pharmaceuticals International
Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation
Ministerio de Ciencia, Innovación y Universidades
Mylan
Cancer Research UK
National Institute for Health and Care Research
Tenovus
European Commission
National Research Foundation
Deutscher Akademischer Austauschdienst
Deutsche Forschungsgemeinschaft
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
Hong Kong Baptist University
Bundesministerium für Bildung und Forschung
Austrian Science Fund
Seoul National University
Universität Wien
Gazi Üniversitesi
Ministero dell’Istruzione, dell’Università e della Ricerca
Türkiye Bilimler Akademisi
China Scholarship Council
Österreichische Forschungsförderungsgesellschaft
Ministério da Ciência, Tecnologia e Ensino Superior
Unitatea Executiva pentru Finantarea Invatamantului Superior, a Cercetarii, Dezvoltarii si Inovarii
Een Häerz fir kriibskrank Kanner
Uniwersytet Medyczny w Lublinie
Recherches Scientifiques Luxembourg
Servier
Universität Innsbruck
Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición
Nestec
Esperion Therapeutics
National Institute for Health Research Southampton Biomedical Research Centre
National Institutes of Health
Directorate for Biological Sciences
Abbott Vascular
Bayer Consumer Health
Medical Research Council
Engineering and Physical Sciences Research Council
Biotechnology and Biological Sciences Research Council
Economic and Social Research Council
Fundação para a Ciência e a Tecnologia
Instituto de Salud Carlos III
Narodowe Centrum Badań i Rozwoju
European Regional Development Fund
Erasmus+
UCB Pharma