A potent and selective reaction hijacking inhibitor of Plasmodium falciparum tyrosine tRNA synthetase exhibits single dose oral efficacy in vivo

• Stanley C. Xie ,

  Contributed equally to this work with: Stanley C. Xie, Chia-Wei Tai

  Roles Conceptualization, Formal analysis, Funding acquisition, Investigation, Writing – original draft, Writing – review & editing

  Affiliations Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria, Australia, Drug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia

  https://orcid.org/0000-0001-7003-4677

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• Chia-Wei Tai ,

  Contributed equally to this work with: Stanley C. Xie, Chia-Wei Tai

  Roles Conceptualization, Formal analysis, Investigation, Writing – original draft, Writing – review & editing

  Affiliation Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria, Australia

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• Craig J. Morton,

  Roles Conceptualization, Formal analysis, Investigation, Writing – original draft, Writing – review & editing

  Affiliation Biomedical Manufacturing Program, CSIRO, Clayton South, Victoria, Australia

  ⨯
• Liting Ma,

  Roles Conceptualization, Formal analysis, Investigation, Writing – original draft, Writing – review & editing

  Affiliation Takeda Development Center Americas, Inc., Cambridge, Massachusetts, United States of America

  ⨯
• Shih-Chung Huang,

  Roles Formal analysis, Investigation, Writing – review & editing

  Affiliation Takeda Development Center Americas, Inc., Cambridge, Massachusetts, United States of America

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• Sergio Wittlin,

  Roles Conceptualization, Formal analysis, Funding acquisition, Investigation, Writing – original draft, Writing – review & editing

  Affiliations Swiss Tropical and Public Health Institute, Allschwil, Switzerland, University of Basel, Basel, Switzerland

  ⨯
• Yawei Du,

  Roles Formal analysis, Investigation, Writing – review & editing

  Affiliation Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria, Australia

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• Yongbo Hu,

  Roles Formal analysis, Investigation, Writing – review & editing

  Affiliation Takeda Development Center Americas, Inc., Cambridge, Massachusetts, United States of America

  ⨯
• Con Dogovski,

  Roles Conceptualization, Formal analysis, Investigation, Writing – review & editing

  Affiliation Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria, Australia

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• Mina Salimimarand,

  Roles Formal analysis, Investigation, Writing – original draft, Writing – review & editing

  Affiliation School of Chemistry, The University of Melbourne, Melbourne, Victoria, Australia

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• Robert Griffin,

  Roles Formal analysis, Investigation, Writing – review & editing

  Affiliation Takeda Development Center Americas, Inc., Cambridge, Massachusetts, United States of America

  ⨯
• Dylan England,

  Roles Formal analysis, Investigation, Writing – review & editing

  Affiliation Takeda Development Center Americas, Inc., Cambridge, Massachusetts, United States of America

  ⨯
• Elisa de la Cruz,

  Roles Formal analysis, Investigation, Writing – review & editing

  Affiliation Takeda Development Center Americas, Inc., Cambridge, Massachusetts, United States of America

  ⨯
• Ioanna Deni,

  Roles Formal analysis, Investigation, Writing – review & editing

  Affiliations Center for Malaria Therapeutics and Antimicrobial Resistance, Columbia University Medical Center, New York, New York, United States of America, Department of Microbiology and Immunology, Columbia University Medical Center, New York, New York, United States of America

  ⨯
• Tomas Yeo,

  Roles Formal analysis, Investigation, Writing – review & editing

  Affiliations Center for Malaria Therapeutics and Antimicrobial Resistance, Columbia University Medical Center, New York, New York, United States of America, Department of Microbiology and Immunology, Columbia University Medical Center, New York, New York, United States of America

  ⨯
• Anna Y. Burkhard,

  Roles Formal analysis, Investigation, Writing – review & editing

  Affiliations Center for Malaria Therapeutics and Antimicrobial Resistance, Columbia University Medical Center, New York, New York, United States of America, Department of Microbiology and Immunology, Columbia University Medical Center, New York, New York, United States of America

  ⨯
• Josefine Striepen,

  Roles Formal analysis, Investigation, Writing – review & editing

  Affiliations Center for Malaria Therapeutics and Antimicrobial Resistance, Columbia University Medical Center, New York, New York, United States of America, Department of Microbiology and Immunology, Columbia University Medical Center, New York, New York, United States of America

  ⨯
• Kyra A. Schindler,

  Roles Formal analysis, Investigation, Writing – review & editing

  Affiliations Center for Malaria Therapeutics and Antimicrobial Resistance, Columbia University Medical Center, New York, New York, United States of America, Department of Microbiology and Immunology, Columbia University Medical Center, New York, New York, United States of America

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• Benigno Crespo,

  Roles Formal analysis, Investigation, Writing – review & editing

  Affiliation Global Health Medicines R&D, GSK, Tres Cantos, Madrid, Spain

  ⨯
• Francisco J. Gamo,

  Roles Conceptualization, Funding acquisition, Writing – review & editing

  Affiliation Global Health Medicines R&D, GSK, Tres Cantos, Madrid, Spain

  ⨯
• Yogesh Khandokar,

  Roles Formal analysis, Investigation, Writing – review & editing

  Affiliation ANSTO-Australian Synchrotron, Clayton, Victoria, Australia

  ⨯
• Craig A. Hutton,

  Roles Conceptualization, Funding acquisition, Writing – original draft, Writing – review & editing

  Affiliation School of Chemistry, The University of Melbourne, Melbourne, Victoria, Australia

  ⨯
• Tayla Rabie,

  Roles Formal analysis, Investigation, Writing – review & editing

  Affiliation Department of Biochemistry, Genetics and Microbiology, University of Pretoria Institute for Sustainable Malaria Control, University of Pretoria, Hatfield, South Africa

  ⨯
• Lyn-Marié Birkholtz,

  Roles Formal analysis, Funding acquisition, Writing – review & editing

  Affiliation Department of Biochemistry, Genetics and Microbiology, University of Pretoria Institute for Sustainable Malaria Control, University of Pretoria, Hatfield, South Africa

  ⨯
• Mufuliat T. Famodimu,

  Roles Formal analysis, Investigation, Writing – review & editing

  Affiliation Department of Infection Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom

  ⨯
• Michael J. Delves,

  Roles Formal analysis, Investigation, Writing – review & editing

  Affiliation Department of Infection Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom

  ⨯
• Judith Bolsher,

  Roles Formal analysis, Investigation, Writing – review & editing

  Affiliation TropIQ Health Sciences, Nijmegen, The Netherlands

  ⨯
• Karin M. J. Koolen,

  Roles Formal analysis, Investigation, Writing – review & editing

  Affiliation TropIQ Health Sciences, Nijmegen, The Netherlands

  ⨯
• Rianne van der Laak,

  Roles Formal analysis, Investigation, Writing – review & editing

  Affiliation TropIQ Health Sciences, Nijmegen, The Netherlands

  ⨯
• Anna C. C. Aguiar,

  Roles Formal analysis, Investigation, Writing – review & editing

  Affiliation Federal University of São Paulo, São Paulo, São Paulo, Brazil

  ⨯
• Dhelio B. Pereira,

  Roles Formal analysis, Investigation, Writing – review & editing

  Affiliation Research Center for Tropical Medicine of Rondonia, Porto Velho, Brazil

  ⨯
• Rafael V. C. Guido,

  Roles Formal analysis, Funding acquisition, Writing – review & editing

  Affiliation Sao Carlos Institute of Physics, University of São Paulo, São Carlos, Brazil

  ⨯
• Darren J. Creek,

  Roles Funding acquisition, Writing – review & editing

  Affiliation Drug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia

  ⨯
• David A. Fidock,

  Roles Conceptualization, Formal analysis, Funding acquisition, Writing – original draft, Writing – review & editing

  Affiliations Center for Malaria Therapeutics and Antimicrobial Resistance, Columbia University Medical Center, New York, New York, United States of America, Department of Microbiology and Immunology, Columbia University Medical Center, New York, New York, United States of America, Division of Infectious Diseases, Department of Medicine, Columbia University Medical Center, New York, New York, United States of America

  ⨯
• Lawrence R. Dick,

  Roles Conceptualization, Formal analysis, Writing – original draft, Writing – review & editing

  Affiliation Seofon Consulting, Natick, Massachusetts, United States of America

  ⨯
• Stephen L. Brand,

  Roles Conceptualization, Formal analysis, Writing – original draft, Writing – review & editing

  Affiliation Medicines for Malaria Venture, Geneva, Switzerland

  ⨯
• Alexandra E. Gould,

  Roles Conceptualization, Formal analysis, Funding acquisition, Writing – original draft, Writing – review & editing

  Affiliations Takeda Development Center Americas, Inc., Cambridge, Massachusetts, United States of America, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America

  ⨯
• Steven Langston ,

  Roles Conceptualization, Formal analysis, Funding acquisition, Writing – original draft, Writing – review & editing

  * E-mail: Steve.Langston@takeda.com (SL); mgriffin@unimelb.edu.au (MDWG); ltilley@unimelb.edu.au (LT)

  ¶‡ These authors jointly supervised this work.

  Affiliation Takeda Development Center Americas, Inc., Cambridge, Massachusetts, United States of America

  ⨯
• Michael D. W. Griffin ,

  Roles Conceptualization, Formal analysis, Funding acquisition, Writing – original draft, Writing – review & editing

  * E-mail: Steve.Langston@takeda.com (SL); mgriffin@unimelb.edu.au (MDWG); ltilley@unimelb.edu.au (LT)

  ¶‡ These authors jointly supervised this work.

  Affiliation Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria, Australia

  ⨯
•  [ ... ],
• Leann Tilley

  Roles Conceptualization, Formal analysis, Funding acquisition, Writing – original draft, Writing – review & editing

  * E-mail: Steve.Langston@takeda.com (SL); mgriffin@unimelb.edu.au (MDWG); ltilley@unimelb.edu.au (LT)

  ¶‡ These authors jointly supervised this work.

  Affiliation Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria, Australia

  https://orcid.org/0000-0001-9910-0199

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