Please use this identifier to cite or link to this item:
https://www.arca.fiocruz.br/handle/icict/67840
NOVEL TRANSMISSION-BLOCKING ANTIMALARIALS IDENTIFIED BY HIGH-THROUGHPUT SCREENING OF PLASMODIUM BERGHEI OOKLUC
Author
Affilliation
Fundação Oswaldo Cruz. Fiocruz Rondônia. Laboratório de Entomologia. Plataforma de Produção e Infecção de Vetores da Malária. Porto Velho, RO, Brasil / Fundação Universidade Federal de Rondônia. Programa de pós-graduação em Biologia Experimental. Porto Velho, RO, Brasil.
Fundação Oswaldo Cruz. Fiocruz Rondônia. Laboratório de Entomologia. Plataforma de Produção e Infecção de Vetores da Malária. Porto Velho, RO, Brasil.
Fundação Oswaldo Cruz. Fiocruz Rondônia. Laboratório de Entomologia. Plataforma de Produção e Infecção de Vetores da Malária. Porto Velho, RO, Brasil / Fundação Universidade Federal de Rondônia. Programa de pós-graduação em Biologia Experimental. Porto Velho, RO, Brasil.
University of São Paulo. Institute of Biomedical Sciences. Department of Parasitology. São Paulo, SP, Brasil.
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Malaria and Vector Research. Rockville, USA.
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Malaria and Vector Research. Rockville, Maryland, USA.
University of São Paulo. Institute of Biomedical Sciences. Department of Parasitology. São Paulo, SP, Brasil.
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Malaria and Vector Research. Rockville, Maryland, USA.
National Institutes of Health. National Center for Advancing Translational Sciences. Division of Preclinical Innovation. Rockville, Maryland, USA.
National Institutes of Health. National Center for Advancing Translational Sciences. Division of Preclinical Innovation. Rockville, Maryland, USA.
University of São Paulo. Institute of Biomedical Sciences. Department of Parasitology. São Paulo, SP, Brasil.
Fundação Oswaldo Cruz. Fiocruz Rondônia. Laboratório de Entomologia. Plataforma de Produção e Infecção de Vetores da Malária. Porto Velho, RO, Brasil.
Fundação Oswaldo Cruz. Fiocruz Rondônia. Laboratório de Entomologia. Plataforma de Produção e Infecção de Vetores da Malária. Porto Velho, RO, Brasil / Fundação Universidade Federal de Rondônia. Programa de pós-graduação em Biologia Experimental. Porto Velho, RO, Brasil.
University of São Paulo. Institute of Biomedical Sciences. Department of Parasitology. São Paulo, SP, Brasil.
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Malaria and Vector Research. Rockville, USA.
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Malaria and Vector Research. Rockville, Maryland, USA.
University of São Paulo. Institute of Biomedical Sciences. Department of Parasitology. São Paulo, SP, Brasil.
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Malaria and Vector Research. Rockville, Maryland, USA.
National Institutes of Health. National Center for Advancing Translational Sciences. Division of Preclinical Innovation. Rockville, Maryland, USA.
National Institutes of Health. National Center for Advancing Translational Sciences. Division of Preclinical Innovation. Rockville, Maryland, USA.
University of São Paulo. Institute of Biomedical Sciences. Department of Parasitology. São Paulo, SP, Brasil.
Abstract
Safe and effective malaria transmission-blocking chemotherapeutics would allow a community-level approach to malaria control and eradication efforts by targeting the mosquito sexual stage of the parasite life cycle. However, only a single drug, primaquine, is currently approved for use in reducing transmission, and drug toxicity limits its widespread implementation. To address this limitation in antimalarial chemotherapeutics, we used a recently developed transgenic Plasmodium berghei line, Ookluc, to perform a series of high-throughput in vitro screens for compounds that inhibit parasite fertilization, the initial step of parasite development within the mosquito. Screens of antimalarial compounds, approved drug collections, and drug-like molecule libraries identified 185 compounds that inhibit parasite maturation to the zygote form. Seven compounds were further characterized to block gametocyte activation or to be cytotoxic to formed zygotes. These were further validated in mosquito membrane-feeding assays using Plasmodium falciparum and P. vivax. This work demonstrates that high-throughput
screens using the Ookluc line can identify compounds that are active against the two most relevant human Plasmodium species and provides a list of compounds that can be explored for the development of new antimalarials to block transmission.
Share